Glutathione deficiency has been linked to many chronic diseases. Diseases such as Alzheimer’s disease, Parkinson’s disease, schizophrenia, bipolar disorder, hepatitis, cystic fibrosis, HIV infection and AIDS, cancer, heart disease, stroke, macular degeneration, asthma, COPD, and diabetes are all linked to oxidative damage and glutathione deficiency. Glutathione deficiency allows oxidative damage to accelerate the progression of these conditions. Let’s take a closer look at some of these health conditions.
Alzheimer’s disease and Parkinson’s disease are both conditions that typically affect older adults. Both of these conditions are the result of oxidative damage. One of the underlying biochemical events in Parkinson’s disease is the depletion of glutathione in affected neurons. This depletion allows oxidative stress to create mitochondrial dysfunction, and finally neuronal cell death. Pre-clinical studies have shown that herbal sources of glutathione reverse this mitochondrial oxidative damage and prevent neuronal cell death. Some drugs developed to treat Parkinson’s disease work, in large part, by increasing glutathione levels and glutathione activity in nerve tissue. Alzheimer’s disease is another neurological condition that is the result of oxidative damage. Oxidative stress increases myloid-beta peptides in the brain. These peptides are involved in the disease process of Alzheimer’s. Neurons with depleted glutathione are much more susceptible to oxidation and the buildup of myloid-beta peptides. Adequate glutathione can exert preventive actions and has a role in the management of both Parkinson’s and Alzheimer’s disease.
Various psychiatric conditions are also made worse by oxidative damage. Brain glutathione levels are decreased in schizophrenia, a disorder that often is chronic and resistant to treatment. A six month randomized, multicenter, double-blind, placebo-controlled study looked at the safety and effectiveness of oral n-acetyl cysteine (NAC) as a source of glutathione in 140 adults with schizophrenia. The study found that taking NAC was a safe and moderately effective strategy for raising glutathione and, in doing so, improving the response to medication in chronic schizophrenia.
The role of oxidative stress in bipolar disorder has become increasingly recognized as an important factor in this illness. People with active bipolar disorder have unregulated glutathione activity which is thought to be a compensatory response to the high oxidative stress. Unfortunately, if these individuals’ glutathione stores become depleted, their bipolar symptoms are likely to worsen. Glutathione depletion is a very real possibility in people with bipolar disorder as some people with this condition attempt to ‘self-medicate’ their symptoms with excessive alcohol or sugar consumption. They may also be prone to tobacco addiction. All of these activities strain glutathione reserves, and, over time, will contribute to glutathione deficiency. In turn, this deficiency will aggravate the symptoms of bipolar disorder.
The development of various cancers has also been linked to glutathione deficiency. The risk of oral cancer is reduced by more than 50 percent in individuals with the highest blood levels (>5.9mmol/g Hb) of glutathione compared to those with the lowest levels (<4.9mmol/g Hb). A similar association has been found for pharyngeal cancer. Men and women who consumed the greatest daily amount of glutathione in their diet (50 to 242 mg) had a more than 50 percent reduction in their risk of developing pharyngeal cancer compared to those with the lowest intake (5mg -33mg). Low levels of glutathione have also been linked to the development of cancers of the colon, prostate, breast, and bladder.
Viral diseases are closely linked to glutathione deficiency. Peoplewith hepatitis, HIV infection,and AIDS characteristically have low glutathione levels.
Chronic oxidative stress and the depletion of endogenous antioxidants play a key role in the development of chronic obstructive pulmonary disease (COPD) and asthma. High oxidative stress coupled with low antioxidant levels increases the risk of developing bronchial asthma and COPD. It can also make these chronic conditions worse, primarily because of a decrease in glutathione activity. This may also explain why certain people with asthma are vulnerable to having asthma attacks from heavy exercise. Exercise creates significant oxidative stress. In asthmatics whose glutathione levels are depleted, this additional oxidative event can be enough to trigger an attack. A similar phenomenon is seen in people with COPD. Systemic inflammation and oxidative stress are associated with muscle wasting and muscle dysfunction in people with COPD, particularly when their glutathione stores are used up.
Viral diseases are closely linked to glutathione deficiency. People with hepatitis, HIV infection, and AIDS characteristically have low glutathione levels. The role of antioxidants in the course of these viral infections can seem confusing. Initially, infection with these viruses requires immune cell destruction via oxidative damage. Additionally, some of the anti-viral medications used to treat these diseases stimulate the oxidative processes in order to destroy the virally infected cells. Thus, an oxidative immune response is needed, not an antioxidant defense. However, as hepatitis and AIDS viral diseases progress, their symptoms are mediated by oxidative damage. Hepatitis C infection, for example, significantly lowers vitamin C and glutathione levels. To make matters worse, treatment with ribavirin (a commonly used anti-viral medication for hepatitis) further reduces the activity of glutathione peroxidase (and superoxide dismutase). Thus, both the infection and its treatment elevate oxidative stress in hepatitis. This elevated oxidative stress, in turn, causes the much feared liver fibrosis and ultimately cirrhosis that can occur as a result of chronic hepatitis. Oxidative stress is also implicated in many of the disease manifestations of AIDS such as dementia, muscle wasting, opportunistic infections, cancers and liver dysfunction. Glutathione depletion is, unfortunately, commonly found in people with AIDS. Addressing their crippled antioxidant defense system is critical to reducing the myriad of symptoms that this disease causes.
Glutathione status is closely tied to the progression and severity of diabetes. In fact, most of the damage associated with diabetes is oxidative damage. High levels of circulating glucose (blood sugar) presents a significant oxidative challenge to the body. In poorly controlled diabetics, elevated blood sugars react with protein amino acids to form reactive proteins. These compounds (advanced glycation end products) create oxidative damage to blood vessels, namely in the eyes and in the kidney. Unless interrupted, this damage will ultimately lead to blindness and to renal failure. Adding insult to injury is the fact that many diabetics will, over time, develop a glutathione deficiency. One study of adolescents with poorly controlled type 1 diabetes mellitus found these individuals to have significant depletion of blood glutathione. This depletion occurs because glutathione is required to mitigate the oxidative damage. Unfortunately, consumption of glutathione-rich foods and even glutathione precursors such as n-acetyl cysteine may not raise glutathione levels in diabetics. This may be because diabetics have impaired ability to utilize these precursors to make glutathione.
Macular degeneration is another condition that is the result of oxidative damage, and a condition that is responsive to glutathione. Age-related macular degeneration is the most common cause of vision loss in people over 50 years old. Macular degeneration occurs as yellow deposits called drusen accumulate between the retinal pigment epithelium and the underlying choroid layer of the eye. Over time, drusen accumulation can result in vision loss in the center of the visual field (the macula). One factor influencing the progression of this disease is oxidation and glutathione deficiency. Given the high exposure to sunlight and to oxygen in the air, the eye is particularly prone to oxidative damage. Antioxidant protection is of critical importance in maintaining eye health. Retinal deterioration occurs when there is an insufficient level of the free radical scavenger glutathione. Oxidative mechanisms are considered to contribute to the aging changes that underlie age-related macular degeneration. Individuals with glutathione deficiency are particularly at risk for the development of macular degeneration.
Glutathione deficiency allows oxidative damage to accelerate the progression of many chronic diseases.
Oxidative stress is now recognized as a key event in the development of coronary artery diseases such as atherosclerosis. An initial oxidative injury to a blood vessel triggers a healing response which involves creating a cholesterol-rich cap over the area of injury. Unfortunately, this healing response can perpetuate itself and ultimately lead to the buildup of fatty plaque deposits on the artery wall. The plaques can become large enough to block the flow of blood. Also, over time, portions of these plaques harden and can break off, forming a thrombus (blood clot). A thrombus can lodge itself in a blood vessel and impede the flow of blood through that vessel. Once blood flow is blocked, the tissues that require that blood will be deprived of nutrients and oxygen. When arterial blockage happens in a vessel supplying blood to the brain, a stroke can result. When blood vessel occlusion happens in an artery supplying a portion of the heart, a heart attack occurs. Obviously these are very serious consequences of cardiovascular disease, which, for many individuals could be avoided.
Cardiovascular disease is largely a preventable disease. Since oxidative injury to the blood vessel is the initial step in cardiovascular disease, it only makes sense that sufficient antioxidant defense is necessary to deter the damage. The role of glutathione in this protection is important. One clinical study showed that low dose NAC (a precursor to glutathione) effectively reduces myocardial oxidative stress in patients undergoing coronary bypass surgery. Glutathione-based antioxidation also plays a key role in helping to prevent the neurological consequences of ischemic stroke (lack of blood supply to affected areas of the brain). When alpha-lipoic acid, a precursor to glutathione, is given to stroke victims, improvement in their neurological function is noted. Glutathione thus plays an important role in both the tolerance to ischemia and in the prevention of ischemic stroke.
Cystic fibrosis is a genetic condition, characterized by thick mucus build-up in the lungs as well as other organs such as bile ducts and intestines. People with cystic fibrosis suffer from difficulty breathing, pneumonia, and numerous other illnesses. The role of glutathione in cystic fibrosis cannot be overstated. Glutathione production and secretion by lung cells is impaired in cystic fibrosis. Lack of glutathione leads to free radical-induced chronic inflammation and infection. Several studies have investigated the use of inhaled glutathione as a treatment for cystic fibrosis. Glutathione inhalation improves lung capacity and results in greater ease of breathing. Inhaled glutathione therapy is well tolerated by people with cystic fibrosis and appears to have minimal to no side effects.
Aging is associated with a depletion of glutathione. Oxidative tissue damage, particularly to the mitochondria, is now a widely accepted explanation for aging. Intracellular glutathione is one of the most important antioxidants to prevent this oxidative aging process. Various animal studies have found that aged animals have lower glutathione levels in all of their major organs than young animals. This decline in tissue glutathione is associated with a decline in the function of those organs. This same phenomenon has been observed in adults. People with chronic kidney disease have very low levels of glutathione in their kidneys and, as the kidney damage progresses, the ability of the kidney cells to make glutathione decreases even further. This creates a vicious cycle of continued kidney damage.
As we age, our production of glutathione decreases in all cells. Sixty-year olds have significantly less glutathione in their blood than 20-year olds. Also, as we age, we may inadvertently do things which empty out our glutathione stores. Many older people experience various body aches and pains and turn to anti-inflammatory medications for relief. Unfortunately, frequent use of acetaminophen (Tylenol), a commonly used anti-inflammatory, depletes glutathione. A low glutathione level in older adults worsens their health status in many more ways than experiencing pain. Older people with deficient glutathione feel unhealthy overall. This is because the decline in antioxidant protection associated with aging is coupled with the effects of cumulative oxidative damage from a lifetime of exposure to free radicals. The net result is chronic disease and poor health.
Glutathione is the most prevalent antioxidant in our cells. When glutathione levels become depleted, our cells are even more vulnerable to the ravages of oxidative damage. While the majority of glutathione in our body is made within our cells, in cases of glutathione depletion, boosting glutathione levels from exogenous sources may be necessary.