Injectable Glutathione

June 15, 2020

, 9:32 am

, Pharmacology

Glutathione (GSH)

A tripeptide made up of glutamic acid, cysteine, and glycine. When these three amino acids are
combined into GSH we see a combination of potential beneficial effects begin to pile up. Remember that
every cell and tissue in our body has the ability to utilize Glutathione as a traditional anti-oxidant (along
with certain tissues/cells having specific benefits that only pertain to them.) Please keep in mind we are
strictly talking about injectable glutathione. Oral glutathione supplementation proves to be very
unreliable at producing results and has very poor bioavailability (it still has the potential to increase
glutathione stores, however, it will almost always need to be degraded into L-cysteine for absorption.)
Glutathione is synthesized intracellularly, and while it can be effluxed from a cell it tends to be
hydrolyzed to its constituent amino acids to then be taken back up by cells and resynthesized
intracellularly into glutathione. We see the process of looking somewhat like this:

γ-glutamyl transpeptidase cleaves the bond —> produces a cysteine-glycine dipeptide and γ-glutamyl
moiety —> that is bound to another amino acid for transport —> once it reaches tissue the γ-
glutamylamino acid is cleaved —> produces 5-oxoproline —> which then gets converted into glutamine.

We then have other interactions going on with glutathione S-transferase (GST) enzymes which are
correlated with GSH’s ability to “remove toxins” from the body but we won’t go in-depth there, just
understand it is another complex enzymatic process to leads to one of the very important benefits of
GSH. Now we can get onto some of the benefits of GSH since you have a basic understanding of this
tripeptide.

MITOCHONDRIA

GSH is the main non-protein thiol in cells whose functions are dependent on the redox-active thiol of its
cysteine moiety that serves as a cofactor for a number of antioxidants and detoxifying enzymes. When
we look at GSH, we see it is distributed into mitochondria where it plays a massive role in against
respiration-induced reactive oxygen species and in the detoxification of lipid hydroperoxides and
electrophiles. Even further more than that, we see the interplay between apoptosis and how
mitochondrial GSH has been shown to critically regulate the level of sensitization to secondary hits that
induce mitochondrial membrane permeabilization and release of proteins confined in the
intermembrane space that once in the cytosol engage the molecular machinery of cell death. Before we
move on, however, we need to take a step back and look at mitochondria. Mitochondria within our cells
generate most of the cellular energy by means of the oxidative phosphorylation (OXPHOS) that is
essential for myriad cellular functions. OXPHOS provides an efficient mechanism to couple electron
transport to synthesize ATP from ADP. Mitochondria are also involved in key cellular functions such as:

Ca2+ homeostasis

heme biosynthesis

nutrient metabolism

steroid hormone biosynthesis

removal of ammonia

integration of metabolic and signaling pathways for cell death and autophagy

in initiating signals in response to metabolic and genetic stress which affects nuclear gene expression,
causing changes in cell function

And the list literally goes on and on (and I hope some keywords in there jumped out at you as pretty
damn important when it comes to maximizing performance, physique development, and end/ultimate
fates of “health.”) Remember that they also contain multiple copies of their own genome as this has
massive interplay with the OXPHOS and respiratory chain. So even though the main function of
mitochondria is to generate ATP, they are the primary intracellular site of oxygen consumption and the
major source of ROS. This is why mitochondrial glutathione (mGSH) is so freaking important! Our
biological system is plastic. It can and will adapt to any imposed demand, period. That means that as we
increase our “number” of muscle cells, androgen receptors, etc we need to also pay special focus on our
ability to increase our mitochondrial density/number as the two go hand in hand. Mitochondria +
Androgens + Imposed Training Adaptations + Altering Nutritional Strategies + Perfected Restoration
Method we could literally go on and on here and you can see a line being drawn connecting everything
together.

This is one of the reasons why I and numerous other individuals talk about “volume” and “progressive
tension overload” as being the catch-all terms that, although extremely valid, make a lot of people these
days stop thinking any further than that. Individuals stop researching beyond the basics because that’s
the only thing that people generally talk about (and that’s perfectly fine, but that’s not me.) This is why
the increasing cross-sectional area of skeletal muscle tissue is a by-product of DOZENS of factors and its
not simply one. We can achieve bigger muscles through a variety of methods and means which is exactly
why so many people can grow despite having wildly drastic training protocols. Androgenic Anabolics
Steroids preferentially hypertrophy type 1 muscle fibers —> Type 1 muscle fibers (due to basic survival
mechanisms) have to produce more mitochondria in order to meet the demand being imposed on our
body —> that leads to more ATP production —> which leads to increased respiration —> which leads to
the need to remove metabolic waste…see where I’m going with this? I do not want to make this into a
training article but in my mind, it all makes sense and is very much connected (and that’s without even
going into the interactions with Type 2 muscle fibers and mitochondria and skimming over the type 1
interactions.) The point I’m trying to hammer home here is GSH, when introduced in an injectable
format, has massive carry over for individuals trying to add muscle tissue to their frame. From its actually
downstream anabolic methods via proper signaling factors to its downstream anti-catabolic methods via
driving restoration, GSH has its place in a bodybuilder’s regimen.

Before we get into the practical application side of things just some random shit no one probably cares
about but I’ll touch on it anyway. Obviously GSH is a massive anti-oxidant and health/longevity aid but it
also has other interactions with fertility and autism. Fertility wise, glutathione (via its action of reducing
oxidative stress) actually enhances morphology and motility of sperm. Longevity wise (just because I
mentioned it) it obviously is looking at that sheer action of reducing oxidative stress and the positive
effects it has on mitochondria. Finally, its interaction with autism is very interesting! It seems that many
individuals that have autism also have elevated levels of certain oxidative metabolites and “anti-
minerals” leading them to be in a somewhat more pro-oxidative state. Glutathione has been and is still
being researched in this population and there holds tremendous promise for these individuals. Either
way, just come off the cuff research I’ve stumbled across that makes a lot of “common” sense when you
just look at the factors and consider the interactions.

Now the practical application side of things is interesting. I want to make this extremely clear that this
dosage is not found in the literature because GSH is not introduced to athletes looking to accelerate
growth/recovery rates. It is generally applied in ill/sick populations that has no carryover to
performance/physique based athletes. But I can say with confidence through all the applications with
clients, myself, and other coaches’ input that has trialed this with their clients (actually only one and its
obviously my best friend Andrew Triana), that dosages will fall in the below ranges depending on your
goal.

Drive “health” (meaning at the onset of sickness apply this amount and 9 times out of 10 your immune
system will do the rest and you’ll avoid getting common illnesses spread at work, school, whatever): 2-
3mg/kg
Drive restoration/mitochondrial growth processes (very self explanatory): 4-8mg/kg

A very big note is that GSH is to be used INFREQUENTLY. This is not something I am a fan of using daily or
even multiple times per week unless you have a tremendous amount of experience with this compound.
GSH is an extremely powerful anti-oxidant and given all its other interactions, makes it so a physique or
performance-based athlete chasing optimal strength or body composition adaptations should not use it
on a frequent basis. I have had a handful of individuals volunteer to trial this theory and the results are
essentially what you would equate to the famous NSAID studies where, on a cellular level, we’re missing
out on certain inflammatory factors/processes that drive those positive adaptations we are looking for
(keep in mind these were 10-20mg/kg dosages per day but the take-home message stays true.) I am the
biggest fan of utilizing GSH 1-2x per week when restoration and full recovery are needed (the morning of
a rest day after a few accumulated days of hard workouts for example.) Again, this portion is not an exact
science but the elevation in recovery, the long term growth potentials, and the ability to raise temporary
“health” can’t be denied.
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