Intracellular Glutathione (GSH):

In support of detoxification we find that the largest concentration of glutathione occurs in the liver. The liver can export glutathione to other areas of the body. The second largest concentration occurs in the epithelial lining fluid of the lungs. This is our major cellular defense where air contamination is concerned. Glutathione is called the master, intracellular antioxidant. Another major role of GSH is to capture the free radicals that are created when the immune system responds to attack. Monoclonal expansion is expansion of our cellular defenses when we suffer an attack against our cells. Free radical production is rapidly increased with cell division and this desire of our immune system to respond to this danger is greatly inhibited unless adequate amounts of glutathione are present.

Another very important role for intracellular glutathione is that of cellular protection against radiation. A recent research article published in the journal Radiology states that “radiation from a single whole-body scan is equal to that from 100 mammograms and is similar to that received by survivors of the atomic bombings of Hiroshima and Nagasaki, Japan – about 1 _ miles from the explosions – according to radiation biolo­gist, David J. Brenner of Columbia University. The radiation from one scan is enough to produce a tumor in one out of 1200 people, and for those who have annual scans the risk increases to one tumor in every 50 people. With inadequate intracellular GSH the risk is greatly increased. The results are self evident in our increasing cancer incident reports.

Detoxification, immune response, antioxidant requirements and protection from radiation caused cellular disease – what more can be said concerning the absolute requirement for maintaining intracellular GSH at 80 to 90% active form per cell?

For cellular repair and regeneration we also depend on the organelles, where our metabolic processes occur to receive protection by the neutralization of free radicals. These free radicals are actually produced by our cellular functions. About 2 to 5% actually escape the normal mechanisms for capture. This is where GSH comes to our rescue. Before the instability of the free radical can stabilize itself by damaging the organelles in the cell, glutathione provides a stabilizing hydrogen ion and prevents cellular damage.

The final responsibility of GSH is as a participant in apoptosis. Apoptosis is the programmed cell death that is set into motion when the cell steps out of normal ser­vice to the body. Glutathione is necessary for cellular protection, repair and the very cornerstone for cellular healing. Remember, cellular healing means tissue healing and tissue healing means normal organ function that translates into balance, harmony and health.  

Where does GSH come from?
GSH is synthesized or made inside the cells of the body. The amino acids that make up GSH must be available for GSH production. The amino acid called cysteine is the most difficult for humans to obtain. Therefore, cysteine is called the “rate limiting” amino acid for GSH production. GSH is homeostatically controlled, both outside and inside the cell. Enzyme systems synthesize it, utilize it, and then regenerate it to keep adequate levels available at all times.

Why is GSH so important to/for our body?
Very simple, GSH depletion leads to cell death! Cell death leads to tissue death. We have trillions of cells in our bodies. We have a tremendous ability to compensate for the loss of cells. The problem arises as to the rate of cell death, the replacement of those cells and the health of the cell with less than normal amounts of intracellular GSH.

How does GSH function in our body?
GSH exists in two forms, the active or reduced form (GSH) and the used/now inac­tive oxidized form (GSSG). The GSH/GSSG ratio may be a sensitive indicator of oxidative stress. The reducing power of GSH is a measure of its free-radical scaveng­ing capacity. Reducing power is also the KEY to the multiple actions of GSH at the molecular, cellular, and tissue levels. It is the reducing power of GSH that creates its effectiveness as a systemic antitoxin. The active form of GSH inside the cells is usu­ally around 90% with the oxidized or inactive form rarely exceeding 10%. It is when reduced GSH levels fall and the inactive or oxidized levels rise that the protective capability and therefore the health of the cell declines. Once the GSH/GSSG ratios change significantly, the cell is vulnerable to attack both from internal processes and external dangers, i.e. toxic challenge and microbial attack, just to identify a few.

There are two major functions of GSH, as an antioxidant and a systemic protectant. These functions are identified as important for:

(a) Antioxidant protection within the cell, especially in the nucleus where DNA and RNA must be protected

(b) As a protectant from toxic materials, especially the liver and lung. The liver must break down and conjugate toxic compounds preparing them for excretion/dis­charge from the body. The first two phases of this conjugation or preparation depends on GSH for its completion. In the lung, where the second highest concentration of GSH exists, we are continually under siege from inhaled toxic material. It is in the epithelial lining fluid that GSH waits to actually capture these cell damaging free radicals, before tissue damage occurs and disease ensues. The renal kidney function also needs protection from free radical and toxic chal­lenge. The heart, which has multiple times the mitochondria in each cell produc­ing the energy needed for the continued contraction of that muscle, produces multiple times the free radicals and therefore each free radical must be stabilized by GSH.

(c) The Immune System: GSH also plays a major role in the rapid monoclonal expan­sion/response of our immune system. When a microbial invader presents itself the immune response gears up for the attack and defense of our cells. Whenever rapid cellular replication occurs the energy produced for this replication has, as a byproduct, large numbers of free radicals produced. If these free radicals are not neutralized then damage occurs and the cell is unable to respond to the demands for replication. This especially involves the lymphocytic, NK (natural killer) cell component of our defense system.

GSH is very important in the antigen presenting cells needed for the modulation of Th-1 or helper cells. These cells are extremely important in our defense against viral and cellular cancer changes.

Antioxidant protection within the cell, both in the cysosol and in the nucleus. GSH is called the “master antioxidant” and is produced within the cell. The ROS or reac­tive oxygen species are collectively called free radicals. These ROS are highly reactive substances and if not neutralized will damage or destroy key cellular components such as the cell wall or membrane, DNA or RNA in milliseconds. These ROS are generated in the mitochondria, which are located inside each cell. These mitochon­dria are the batteries that provide the power/energy for the cells to operate. ROS or oxyradicals can also come from environmental chemicals or pollutants, food, impure water as well as radiation of various types. Another major function of GSH is to recycle other antioxidants such as vitamin C, a water phase antioxidant, and vitamin E a lipid phase antioxidant. This reduces these antioxidants so they can go back to capture other free radicals.

How does GSH help the body prevent disease?
The cellular level of GSH changes as you go through the day. Stress, microbial at­tack, cellular cancer change, cellular degenerative change, traumatic change, exercise change, changes of aging, lack of nutritional support and lack of supplementation all effect the homeostatic control mechanism that has the responsibility to maintain effective levels of intracellular GSH.  When the level of GSH declines or the GSH/GSSG ratio changes the cell involved begins to experience damage. Depending on the type of cell involved dictates the type of tissue involved which dictates the organ system involved. Depending on which organ system that suffers will dictate the disease process or type of diseases that then may occur.

Where the cell is involved with oxidative damage you will see these oxidative re­lated diseases: accelerated aging, cell destruction, compromised immune response, cancer, arteriosclerosis, coronary artery disease, Parkinson’s disease, diabetes, cataract formation, macular degeneration, Emphysema/COPD, allergy/asthma, stroke and Alzheimer’s to list only a few.

We discussed the importance of GSH in relation to our immune response. Every day research is uncovering more intricate details of how GSH functions in this very sophisticated integrated response and defense system. It is so very important for each of us to have an immune response that is capable 100%. We are under attack at all times, day and night and it does not take much to alter that response just a few percentage points and then the result can be disastrous.

Some of the immune system related diseases are: viral infections, i.e. sudden acute respiratory syndrome (SARS), hepatitis, HIV/AIDS, herpes, common cold, bacterial super infections, the autoimmune diseases and cancer, just to name a few of the diseases.

In our environment, especially over the last 10 years, the prevalence of environmental toxins has finally been recognized. Recognized not only as secondary to toxins in our air but also in the food we eat and in the liquid we drink. When you breathe, eat or drink you are exposed to disease providing toxins. In fact, current research is identifying and relating intracellular toxic burden with disease, disease that often times cannot be helped by mainstream medicine are being successfully treated by enhancing the body’s ability to convert the damaging chemical substances into harm­less conjugates that the body can eliminate. Once this burden is removed from the cell, a normal function many times can be restored.

Toxic related diseases: Emphysema, liver disease, liver cancer (which many times is a natural progression of compromised liver cells), bladder cancer, kidney and liver failure, colon inflammation and colon cancer and multiple environmental illnesses.

Known toxins include cigarette smoke, carcinogens, auto exhaust, drug usage (both medicinal drugs as well as street drugs), chemotherapy and radiation treatments.

Finally, but not inclusively, some of the radiation related diseases are: skin cancer, DNA damage, eye damage, sunburn and many skin related disorders.

What causes a decline in levels of GSH?
Dietary intake of GSH rich foods is minimal at best. Those people who do not eat live fruits and vegetables but the typical American or western diet, will not increase their GSH levels. Then, as the aging process progresses there is a slow decline in the cellular synthesis of GSH. The GSH “pool” is not infinite and if not replaced or maintained, will result in levels of GSH that cannot carry the burden or responsibil­ity of GSH function.

Exercise causes a decline in intracellular GSH as the GSH is utilized in mitigating the enormous production of free radicals occurring with the exercise process. The free radicals of energy production are increased, respiratory rate is increased so the epithelial lining fluid (ELF) pool of GSH is challenged. The utilization of calories for energy also obligates the GSH pool.

How can I increase my levels of intracellular GSH?
The first step is to evaluate your lifestyle. Are you a smoker? Do you live with sig­nificant stress? Does your diet provide live enzymatically rich fruits and vegetables? Do you supplement with a full spectrum of minerals, vitamins, essential fatty acids and the extracellular antioxidants? This being the foundation of your daily existence you then need to provide the GSH substrates that have been proven to increase the intracellular production or synthesis of GSH. Do not take the free amino acid cyste­ine as that is not delivered to the cell wall where it can be utilized in GSH synthesis. Also, do not waste your money taking glutathione tablets or capsules as these are broken down by the prototeolytic enzymes in the intestinal tract and the glutathione does not reach the cell as glutathione.  GSH Complex®, with the double sulfa bond of cystine, delivers the substrates to the cell wall where it becomes synthesized into intracellular glutathione. GSH as a tripeptide does not traverse the stomach and intestinal tract in large enough amounts to influence the synthesis of GSH in beneficial amounts. Systemic availability of oral GSH is negligible in man, and because there is no evidence for transport of GSH into cells GSH must be synthesized intracellularly. The NAC (N-Acetylcystine) can be used intravenously to increase GSH but only for a few days as the byproduct of this method of delivery actually produces toxins.

Therefore, the proven, non-toxic and safe method to increase intracellular GSH is by utilizing the substrates which produced the glu-cys residues in sufficient amounts to be impactful. What takes place is the cystine in GSH (which is two cysteines linked by a double sulfa bond) released during digestion in the gastrointestinal tract is more stable than the free cysteine, because the disulfide bond is pepsin and trypsin resistant and therefore these enzymes are unable to break down this amino acid during the digestive process. This then allows the cysteine to be delivered to the cell where it is then utilized in the synthesis of GSH.