Reduced glutathione (GSH) is a peptide, meaning it is a compound made up of amino acids. It is also endogenous, meaning it is always in our bodies, and is naturally found in most cells. While our bodies naturally create reduced glutathione, it is not always enough for all of its functions throughout the body. As a key part of regulating oxidative stress and other major bodily functions, it is important to supplement the body’s reduced glutathione supply. All different parts of the body use and contain reduced glutathione but most of the body’s supply is located in the lungs and liver.
Most notably, glutathione supports balanced oxidation levels and immune function. Glutathione exists in two forms. Those forms are reduced glutathione (GSH) and oxidized glutathione (GSSG) and each have their own uses in the body. We have chosen to focus on GSH due to its effects on oxidative stress and other bodily processes that GSSG is unable to attain or may even impact negatively instead.
Even small deficiencies in glutathione can have undesirable effects on the body, so maintaining your glutathione levels with a reduced glutathione supplement is a good idea for practically everyone.
Bioavailability of Reduced Glutathione
The bioavailability of reduced glutathione constantly appears to be under scrutiny, with many people saying that reduced glutathione does not absorb well. While the absorption of reduced glutathione is indeed not stellar, this can very easily be compensated for with a higher dosage. This is why we ended up going for a higher dose (500mg), which should offset the limited bioavailability very well.
In fact, in one 6 month study, participants were given either 250 mg per day or 1,000 mg per day of reduced glutathione. Reduced glutathione levels improved in erythrocytes, plasma, lymphocytes and buccal cells in only 1 month! At the end of the study, the group with the larger dose had 30-35% more reduced glutathione in erythrocytes, lymphocytes and plasma while the smaller dose had 17% more in the blood and 29% more in erythrocytes. These benefits even continued on for the month after participants stopped taking their doses, showing the long-term effects of consistently supplementing reduced glutathione.
Reduced Glutathione Cellular Function Benefits
Reduced glutathione has a remarkable effect on oxidation throughout the body, and with this in mind it is no surprise that it is one of the main endogenous oxidation regulating compounds throughout the body. One of the main ways in which reduced glutathione supports balanced oxidation levels is by directly neutralizing reactive oxygen species (ROS) like superoxide and hydrogen peroxide. When reduced glutathione performs this neutralization reaction with ROS, reduced glutathione itself becomes oxidized, which yields the oxidized form of glutathione known as GSSG. GSSG does not possess the same oxidation regulating effects that reduced glutathione does. In fact, it may even act as a pro-oxidant in some cases.
This is why GSSG levels are under strict control of various enzymes and biochemical processes throughout the body that convert GSSG back to reduced glutathione. This mechanism of action also explains why the body contains such large stores of reduced glutathione and why topping off these glutathione stores with supplemented reduced glutathione can help promote ideal oxidative status throughout the body.
Reduced Glutathione and Oxidation-Regulating Vitamin Regeneration
Not only does reduced glutathione directly neutralize ROS via chemical reactions, it also helps balance oxidation levels through a plethora of other pathways. For example, reduced glutathione helps regenerate vitamin E and vitamin C levels in the body. Both of these essential vitamins also have remarkable effects on oxidation, and thus, by regenerating their levels, the oxidation balancing effects of glutathione extend further than you may imagine! Not only does glutathione help regenerate these oxidation-regulating vitamins, it also functions as a cofactor for endogenous oxidation regulating enzymes such as glutathione peroxidase or glutathione-S-transferase.
Reduced Glutathione and Phase II Detoxification
Reduced glutathione also plays a very important role in phase II detoxification in the liver, which also produces an oxidation-balancing effect. Furthermore, reduced glutathione can also mitigate the oxidative stress produced by enzymes in phase I detoxification in the liver. With this in mind, it becomes clear why reduced glutathione is also often discussed in the context of liver health. That’s because it plays a large role in the primary function of the liver: detoxification. So, it is also no surprise that one of the largest glutathione stores in the body is located in the liver!
Reduced Glutathione and Inflammation
The oxidation-regulating effects also help regulate inflammation. For example, the ROS hydrogen peroxide, which reduced glutathione directly neutralizes, is a form of ROS that also causes significant inflammation in the body. By neutralizing hydrogen peroxide, we can expect to see both an attenuation of oxidation and inflammation. Reduced glutathione also mitigates superoxide, curbing inflammation caused by its oxidative properties within cells, crucial for overall body health.
When taken together, it becomes clear that reduced glutathione has a remarkable effect on promoting cellular health. This is because it attenuates two of the main threats to cellular function: oxidative stress and inflammation. Moreover, its detoxification capabilities safeguard cellular health, shielding cells from ROS, mercury, and persistent organic pollutants, internal and external stressors. Reduced glutathione’s unique ability to regulate melanocyte function distinguishes it from other oxidation-regulating compounds. As far as cellular health goes, supplementing reduced glutathione is a no-brainer!
Reduced Glutathione Skin Health Benefits
Skin health is another benefit that stems directly from reduced glutathione’s regulatory effect on oxidation levels. Our blog on skin health highlights UV radiation from the sun as one of the skin’s major threats. Reduced glutathione, like many other oxidation-regulating compounds can also help protect the skin from UV radiation.
However, reduced glutathione has another trick up its sleeve! When we are exposed to UV radiation, melanocytes are activated and produce melanin. Melanin is a pigment that is largely responsible for our skin tones and is the compound that produces a tan. However, it is also a very important oxidation-regulating compound, thus melanin serves as a protective mechanism against UV exposure. That being said, during prolonged periods of UV exposure, melanocytes can actually become overactive and produce too much melanin. This leads to two undesirable outcomes. The first of which is the generation of hydrogen peroxide, which as we talked about earlier, is a strong ROS. The second of which is localized accumulation of melanin, which can cause freckles and various hyperpigmentation blemishes.
This is where reduced glutathione comes in! Reduced glutathione notably regulates melanocyte function, suppressing activity upon UV exposure. This mechanism reduces melanin overexpression, lowering hydrogen peroxide production and localized hyperpigmentation. Given this, replenish reduced glutathione levels if exposed to prolonged sun exposure.
Reduced Glutathione Immune System Function Benefits
In order to maintain healthy immune function, lymphoid cells need to be functioning properly. Reduced glutathione may support the lymphatic system, integral to immune defense against invaders. Even minor deficiencies in lymphoid cells can have far reaching negative effects on immune function. Reduced glutathione enters lymphocytes, white blood cells combating foreign substances in the body. Once there, reduced glutathione helps promote the activity of lymphocytes. This leads to a promotion of overall immune function. Low reduced glutathione levels profoundly affect the lymphatic and immune systems. This is yet another reason why maintaining adequate body stores of reduced glutathione is very important to overall health!
Reduced Glutathione Respiratory Function Benefits
When not properly caring for cellular inflammation, it can lead to many major issues, such as inflammation of the lungs. Reduced glutathione helps to regulate cellular inflammation via inhibiting the activity of proinflammatory cytokines. Reduced glutathione mitigates ROS, crucial for inflammation as ROS activates proinflammatory cytokines. In other words, via its excellent oxidation regulating effect, reduced glutathione even produces significant inflammation regulating effects! Lung sensitivity to oxidation and inflammation underscores the importance of robust glutathione levels, crucial for respiratory health. Lungs harbor abundant glutathione, unsurprisingly, given its vital role in respiratory health and detoxification within the body. Our lungs clearly need a large amount of reduced glutathione in order to protect delicate structures, such as the alveoli.
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