Hacking the TRIIM Trial and Boosting hGH Levels Without Injections

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by Nils Osmar. Updated Jan. 19, 2024 Medical Disclaimer

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 study was called the TRIIM Trial. TRIIM stands for “Thymus Regeneration, Immunorestoration, and Insulin Mitigation”. A second, larger trial is now underway. In this article, I’ll be talking about an approach I’ve been taking with the intention of approximating the results of the study.

To be clear, I am not recommending that anyone else try hacking TRIIM or follow my protocol, just sharing information about what I’ve been doing.

The compounds used in the study included:

  1. Human growth hormone (hGH) (given by injection)
  2. Metformin
  3. DHEA
  4. Vitamin D3
  5. Zinc

Dose and frequency

According to a recent article on Peter Attia’s website:

In the TRIIM study 9 men, ages 51-65, first took hGH alone (0.015 mg/kg, or ~3 IU for a person weighing 70 kg) 3-4 times per week for one week and then added DHEA (50 mg) the next week, similar to Fahy’s n=1. The week after that, the same doses of hGH and DHEA were combined with metformin (500 mg). At the start of the fourth week, the doses were individualized based on each participant’s particular responses.

(To put the hGH dosing into context, while it’s individualized, athletes using it for performance enhancement may take 10-25 IU 3-4 times a week and “longevity” clinics may prescribe somewhere in the ballpark of 1-2 IU/day.) The goal of this titration approach was to maximize IGF-1 and minimize insulin by varying each of the hormones and drugs. The study didn’t reveal what the effect DHEA hay have had after week 2, so we contacted Fahy to check. He wrote that the results with DHEA were qualitatively the same but quantitatively different, with each person having their own specific response (personal communication, email).

Why these ingredients?

  1. Growth hormone had been shown in numerous animal studies to rejuvenate atrophied thymus glands and restore immune health; this was a test to see if it also worked in humans. See study.
  2. Metformin was included in the study because of an anti-cancer effect (to counteract hGH’s pro-cancer attributes) Also has purported anti-aging effects.
  3. DHEA was included because some studies suggest it has pro-immunity anti-aging effects.
  4. Vitamin D3 had also been shown in animal studies to help rejuvenate the thymus. Participants took 3,000 i.u. of vitamin D3 daily.
  5. Zinc is also associated with immune health, and regulates how the thymus gland produces T cells. According to a 2009 study, “zinc supplementation can reverse some age-related thymic defects and may be of considerable benefit in improving immune function and overall health in elderly populations.” Participants took 50 mg/day.

Results

After two years on the protocol, participants experienced:

  • Regeneration of their thymus glands, verified using MRI scans.
  • Improved immune function 
  • Improved kidney function, illustrated by an increased glomerular filtration rate, or GFR.
  • Signs of increased protection from cancer
  • Improvements in their PSA levels
  • Improvements in their C-reactive protein
  • Signs of regeneration of their kidney function 
  • Signs of regeneration of bone marrow
  • An improved lymphocyte to monocyte ratio
  • 2.5 years of age reversal, as measured by four different DNA methylation tests. (The age reversal was accelerating at the end of the study, with most of it taking place in the last few months, so if the trial had continued, it might have been much greater.)

About epigenetic clocks

When you turn back a household clock, you’re not actually resetting time. (Turning a clock to read 3 pm doesn’t make the time 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

  • The trial had five ingredients, but according to Greg Fahy, hGH injections were the centerpiece. The other compounds were there to buffer and control the possible side effects of hGH injections.
  • hGH, of course, spurs growth in children and adolescents.
  • In adults, hGH 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.  Prior studies on animals had shown that hGH injections restore functioning to involuted thymus glands in animals; TRIIM verified that this effect occurs in humans too.

Concerns about cancer

And at least one of the components used in the trial, synthetic recombinant hGH, is associated with an increased risk of cancer. Fahy’s hope was that giving metformin, DHEA, vitamin D3 and zinc along with hGH injections would prevent this side effect. The results were promising in that no increase in cancer was seen in the original TRIIM trial. But more studies are needed (and are being conducted) to verify the safety of the protocol.

Emulating TRIIM

Might it be possible to “hack” the TRIIM trial if you don’t have access to metformin as a medication or hGH injections? Perhaps.

  • One approach of course would be to get a medical prescription for hGH injections and metformin from an M.D. (such as a so-called “anti-aging doctor”) and take the other compounds  (D3, zinc and DHEA) as supplements. (All are readily available online.)
  • Berberine is similar in some regards to metformin, so some people have suggested substituting it. The two compounds aren’t identical but do have many similar effects in the human body.
  • People who dislike injections might also try raising their hGH by non-pharmaceutical means.
  • Once again, to be clear, I’m not advocating that anyone do so. See the medical disclaimer below

My results

For the results of my protocol, see this page. But bear in mind that I’ve made many changes over the years, above and beyond emulating the TRIIM trial. For example, I’ve started working out and added more animal-based protein to my diet. So I don’t know to what degree my emulation of TRIIM has been a factor. I can say anecdotally that I feel younger and more energetic when I include the elements designed to emulate TRIIM in what I’m doing.

Raising hGH levels with intermittent fasting

  • 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.

… or prolonged fasting

Another way to raise human growth hormones is 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

… or taking saunas (particularly when fasting)

From an older, but still interesting 1984 study:

The increase in plasma GH after heating was partially suppressed in the non-fasting state reaching a mean of 7.9 +/- 3.5 (SEM), ng/ml, range 1.0-36 ng/ml. In contrast all subjects exhibited higher increases, mean 18.3 +/- 4.0 ng/ml, range 7-44 ng/ml, in response to heating when fasting.

Note: Young men appear to respond to heat and saunas better than older men. From a different study:

We conclude that heat exposure-stimulated GH release in young adult men is mediated by GHRH, but in older men, GHRH and GH responses do not occur.

Amino acids

One possible method of raising hGH would be 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 in a 1:1 ratio:

  • 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 arginine and lysine a coup[e of hours after exercising for this reason, rather than right after or before.

Adding other amino acids to the mix appears to improve the situation. According to randomized, placebo-controlled, double-blind, 2020 crossover study, a supplement called SeroVital, containing 2.9 grams of L-lysine, L-arginine, oxo-proline, N-acetyl-l-cysteine, L-glutamine, and schizonepeta, increased hGH levels significantly in both males and females. The exact amounts of each amino acid were revealed. From the study: “At 120 minutes, hGH levels increased by 682% (8-fold) from baseline and were significantly higher than placebo.”

Supplements I’m taking to increase hGH

I take a lot of supplements. The ones associated with a possible increase in hGH are:

  1. Creatine, I take 5 grams daily. According to this study, “In a comparative cross-sectional study, 6 healthy male subjects ingested in resting conditions a single dose of 20 g creatine (Cr-test) vs a control (c-test)…. for the majority of subjects the maximum GH concentration occurred between 2 hrs and 6 hrs after the acute Cr ingestion.” (I take creatine for a variety of reasons; the possible increase in hGH is one of them. However, I don’t take the large triggering dose used in the study.) Note: Taking creatine along with electrolytes increases its absorption as much as five-fold. So I add a spoonful of electrolytes when taking it. See study.
  2. Arginine and Lysine. I take 1200 mg of each. (Their combination, in this dose, raises hGH more than either product taken alone. (See study). Some people substitute L. citrulline for arginine, because our bloodlevels of arginine go higher when taking l. citrulline. I take lysine with l. citrulline, and also take arginine as part of AAKG (a salt of arginine and alpha ketoglutarate) because AKG has also been found to raise hGH levels. See study
  3. Zinc and copperSee study.
  4. Vitamin D3 and K2See study.
  5. Beta Alanine. I sometimes take it before workouts, and sometimes after. From a Healthline article: “In one study, taking 4.8 grams of beta-alanine before a workout increased the number of repetitions performed by 22%. It also doubled peak power and boosted hGH levels compared with the non-supplement group.
  6. DHEA. I take DHEA both as a testosterone booster and hGH booster. In one experiment in rats, it was shown to almost double hGH levels. I take 50-75 mg/day. See study. Caution: some studies suggest a correlation between DHEA consumption and an increase in cancer.

See my full list of supplements

I also take:

  1. Zinc (on days when I’m not eating oysters, which are rich in zinc)
  2. Berberine (an herb which David Sinclair once called “the poor man’s metformin”) (I tried metformin for a while but didn’t care for it.)
  3. Vitamin D3 (in a formula with vitamin K2)
  4. DHEA

One weakness in what I’m doing it that it’s 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, emulate my protocol. What you do is up to you. There arguments against raising hGH levels which I’ll go into below. I’m choosing to raise mine, but I’m also a 69 year old whose levels have presumably dropped since I was in my twenties.

About hGH, IGF-1, and mTOR

There are two growth hormones which people sometimes confuse with each other: hGH and IGF-1.. While both activatate growth pathways, they are not identical. For example, IGF-1 levels drop when we fast, but hGH levels skyrocket (apparently to preserve muscle when no nutrients are coming in).

“Wait. Isn’t hGH Pro-Aging?”

As with many things in the area of longevity, the answer is a little complicated. In this case, we need to start by clarifying the difference between interventions that are life extending and those that show evidence of reversing 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 [69] 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 [70].

Subsequent studies provided new examples of longer survival of shorter people [71] 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.

Caveats about the TRIIM trial

The trial was fascinating (to my mind) but had some problems. Peter 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.

Learn more

Read more about the TRIIM Trial

Testing your epigenetic age

Most tests which purport to read our epigenetic age cost hundreds of dollars. A list of tests and their prices can be found on this page.

A relatively inexpensive way of getting an approximation of your epigenetic age is to use the PhenoAge calculator. Your only cost will be a blood test to find some specific markers. (The cost of the blood test ranges from around$75 to $86.) The results have been found to correlate closely with actual epigenetic tests. More information.

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