A recent study suggests that taking five compounds together can (1) reverse involution of the thymus gland in elderly people; (2) rejuvenate the aging immune system, restoring it to the functioning level of young adults; (3) slow the aging process; and (4) reverse some of the aging that has already occurred – which could possibly extend the human lifespan.
The ingredients used in the study were:
- Human growth hormone (hGH)
- Vitamin D3
Why These Ingredients?
- Human growth hormone (hGH) – had been shown previously in animal studies to rejuvenate atrophied thymus glands and restore immune health; this was a test to see if it also worked in humans.
- Metformin – included in the study because of an anti-cancer effect (to counteract hGH’s pro-cancer attributes) Also has purported anti-aging effects.
- DHEA – some studies suggest it has anti-aging effects
- Vitamin D3 – had also been shown in animal studies to help rejuvenate the thymus
- Zinc – also associated with immune health
When you turn back a household clock, you’re not actually resetting time. (Turning a kitchen clock to read 3 pm doesn’t make the time really 3 pm.)
Epigenetic clocks, based on methylation, are purportedly different. Resetting one actually may be resetting your “internal time”, and could in theory, add years to your life. If you turn your methylation clock back five years, according to Dr. David Sinclair and others, you might (theoretically) be five years “younger” and live five years longer than you would have as a result.
The original TRIIM trial lasted one year. At the end of it, the participants’ thymus glands, which had become involuted (turning them into inert fatty tissue) had all been restored to full functioning. And at the end of the trial they were 2.5 years younger, epigenetically speaking, than they would have been if they had not participated in the trial.
Benefits of raising hGH
- hGH spurs growth in children and adolescents. In adults, it helps to regulate body composition, muscle and bone growth, fat and sugar metabolism, and possibly heart function. It’s used by cells during growth and in healing from injuries and other wounds.
- According to Harvard Medical School, “By age 55, blood levels of growth hormone are about one-third lower than they are in people ages 18 to 35. This drop also coincides with the reduced muscle mass and increased body fat that happens with aging.”
- T-Cells are produced by the thymus gland, and are essential to the functioning of our immune systems. They decline because thymus glands become involuted, a process that goes on for years, leading to the gradual collapse of our immune systems.
hGH Injections and Cancer
And at least one of the components used in the trial, synthetic recombinant hGH, is associated with an increased risk of cancer, not at this point in the people who took part in the study, but in people taking it medically for other reasons. It’s conceivable that I could be increasing my odds of getting cancer by taking supplements known to increase my hGH levels.
Nonetheless, some people in the anti-aging community have been looking into whether it might be possible to emulate the study on their own – raising hGH while taking metformin because of its purported anti-cancer effects.
In my own case, I’m not too worried about the cancer possibility because all I’m aiming for is to increase my hGH to the levels that were in my body when I was a twenty year old. Young people are not more likely to get cancer than older people whose hGH levels have tanked, in fact they’re far less likely. I’m not using injections (the form of hGH administration associated with cancer), but am taking supplements which trigger more hGH production using my own body’s mechanisms.
Note: To prevent cancer, the designer of the TRIIM trial added metformin to the regimen.
Emulating the TRIIM Trial
As it turns out, the trial is an easy one to hack.
- One way of doing so would be to get prescriptions for hGH and metformin from your doctor, if he or she is willing to prescribe them, and take the other compounds as supplements.
- Substituting berberine for metformin is a possible variation on the protocol. The two compounds aren’t identical but do have many similar effects in the human body.
- You could also try raising your hGH by non-pharmaceutical means, as I’m doing. As far as I’ve been able to tell from the readings I’ve done, doing so does not appear to be associated with the same negative effects.
Raising hGH Levels Without Injections
- One method of raising human growth hormone is fasting. According to this Healthline article, “Studies show that fasting leads to a major increase in HGH levels. One study found that 3 days into a fast, HGH levels increased by over 300%. After 1 week of fasting, they had increased by a massive 1,250%”
- Fasting has side benefits, which is that as it raises hGH levels, it lowers insulin and decreases levels of a different growth-related hormone, IGF-1.
- Even a very short fast like skipping dinner every night (not eating before bed) and going to bed around 9:30 or 10 pm (i.e., early rather than late) will raise your HGH levels.
- As a bonus, doing so also raises NAD (nicotinamide adenine dinucleotide), another compound that appears to have anti-aging benefits.
- Longer fasts have even more benefit. In a prolonged fast, hGH levels skyrocket. By 36 hours (the start of a feasting day), your HGH should be up around 200-300 percent of its usual level.
Taking Lysine and Arginine (Together)
A different method is supplementation with amino acids which stimulate the body’s production of hGH. One study found that you can raise your levels significantly by taking these two supplements together:
- 1500 mg lysine
- 1500 mg arginine
Subjects were given lysine and arginine in the amounts shown above, with and without exercising. Their blood levels of hGH were tested 30, 60 and 90 minutes later. At 60 minutes, their hGH levels were “significantly elevated”, but only in the group that had not exercised. Exercise actually negated the benefits of supplementation in this study. I take them after exercise for this reason, rather than before.
Another way to raise human growth hormones to do prolonged fasts of more than 24 hours). One approach would be to do alternate day fasting. I did this for several months in 2020; I fasted all day on Monday, Wednesday and Friday, while working out and feasting on Tuesdays, Thursdays and Saturdays. I put on a significant amount of muscle during this period while losing almost 40 pounds of body fat. I was also taking metformin, DHEA, zinc and vitamin D3 on my non-fasting days.
Supplements that Increase hGH Levels
Amounts are the amount I take on the days when I take these supplements:
- Melatonin – Life Extension – 0.3 mg
- Creatine – Live Extension – 5 capsules
- HMB – Naturebell – 3 capsules
- Beta Alanine – Nutricost – 4 capsules
- L. Citrulline (increases arginine) – Double Wood – 3 grams
- L. lysine – Pure encapsulations – 200 mg.
- Zinc and copper – 30 mg. zinc, 2 mg. copper
- Vitamin D3 (Donotage)
- NAC (N. Acetyl Cysteine) Life Extension – 1200 mg
- Glycine – 1500 mg
- Sulforaphane – Avamocol – 2 tablets
- Milk thistle – 500 mg
- AKG, I’m currently taking AKG in the mornings in the Ca-AKG form. I sometimes also take it in the afternoon as AAKG,
Obviously what I’m doing is not a controlled experiment, just an N=1 exploration to see what happens. I have no way of knowing for sure whether any effects I end up experiencing are due to this protocol.
I’m not saying that everyone has to, or should, take all of these supplements – or even one of two of them – to boost hGH. There arguments against raising hGH levels which I’ll go into below. I’m describing my protocol and how it’s working so far What you take, or don’t take, is completely up to you.
I also Take:
- Metformin (or sometimes berberine)
- Vitamin D3
I was already taking many of these supplements for other reasons, such as taking berberine and/or metformin to control blood glucose. So for me this was more a matter of changing the timing of the supplements than taking something new.
So far I have notice a boost in my energy, both physical and mental.
I should note that these are not the only anti-aging supplements I’m taking; I also take stacks of NAD boosters and testosterone boosters most days. I also take Ca-AKG, which has also been shown in studies in humans and animals to reverse epigenetic aging.
On my “feasting” days, I take the NAD boosters in the morning; then take my testosterone boosters; then work out fasted (i.e, not breakfast yet); then take my version the TRIIM trial cocktail an hour or two later with my first meal.
About hGH, IGF-1, and mTOR
There are two growth hormones which people sometimes confuse with each other: hGH and IGF-1. They’re related but not identical.
For example, eating foods rich in leucine (an animo acid in some proteins) stimulates the production of IGF-1, which can result in faster muscle growth.
IGF-1 levels drop when we fast, but hGH levels skyrocket (apparently to preserve muscle when no nutrients are coming in).
Both hormones are associated with the growth pathway, but their actions aren’t identical in the body. And some studies suggest that raising hGH levels – at least by injection – may actually end up shortening the lifespan.
My strategy is to take hGH boosters on workout days only, shortly after my workouts along with a high protein meal, to switch on mTOR and support muscle growth (and push back against sarcopenia). I’m not trying to activate these pathways full time, but I do want to activate them strongly shortly after exercising on resistance training days. I “feast” on my workout days (after working out) to activate mTOR, knowing my IGF-1 will (temporarily) go up too. I either fast or eat a more plant-based diet on my non-workout days, to keep AMPK activated on those days.
“Isn’t hGH Pro-Aging?”
As with many things in the area of longevity, the answers are complex. In this case, we need to start by clarifying the difference between interventions that are life extending and those that reverse aging (without necessarily extending the human lifespan). Things which activate the growth pathways tend to fall into the latter category.
Human growth hormone is unquestionably pro-growth, and is associated with higher IGF-1, But it’s also associated with the rejuvenation of the thymus gland and the reversal of epigenetic aging. According to a 2019 article entitled “Growth Hormone and Aging: Updated Review“:
The initial evidence for a role of GH signaling in the control of human aging was largely indirect and often considered controversial. Samaras  reported numerous examples of a negative correlation of longevity with height, a GH-dependent trait. However, some examples of taller people living longer were also reported .
Subsequent studies provided new examples of longer survival of shorter people  and uncovered association of polymorphism of genes coding for GH, IGF-1, IGF-1 receptor and their downstream targets, with exceptional longevity.
Reports of remarkably extended longevity in diminutive mice lacking GH or GHR increased interest in aging of humans with the same genetic defects or with dwarfism of different etiologies but few clear answers emerged from these studies.
A Johns Hopkins Medicine article weighs in:
Some studies have suggested that mice whose bodies don’t efficiently produce or process the mouse equivalent to HGH have an extended lifespan.
Other research has shown that people with low levels of HGH due to surgical or radiation damage to the pituitary gland that makes HGH have increased risk of cardiovascular disease, a factor that can shorten life span.
So the truth is, there’s evidence of benefits and drawbacks to increasing hGH. The best strategy (in my estimation) would appear to be one of balance: increasing hGH on days when we want growth, and easing away from it on days when we’re more focused on activating AMPK, autophagy, and the longevity pathways.
Raising hGH Levels on Workout Days
My current approach in terms of hGH is:
- Activating my growth pathways (which involves taking hGH boosters and testosterone boosters and working out) mainly on my resistance training days – the same days that I’m activating mTOR by eating higher protein, more animals-based meals – and:
- Not taking the supplements that increase hGH production on my recovery days, when I’m often also fasting (which activates the AMPK/longevity pathway and switches MTOR (the growth pathway) off.
To learn more about the first TRIIM trial which established a positive correlation between increasing growth hormone and reversing epigenetic aging, click here.
Caveats about this Study
The trial was fascinating (to my mind) but had some problems. Some researchers, such as Peter Attia, are dubious. Attia points out that the study had only nine participants and had poor controls.
A second study, the TRIIM X trial, is being conducted to clarify whether the results hold up in a much larger and more diverse study population. In the meantime, just speaking for myself, the results of the first trial were promising enough that I decided to explore the possibility of hacking it, starting with increasing my natural hGH.
Read more about the TRIIM Trial