Glutathione Regulation and the Importance of Maintaining Balance

Paul L. Reller L.Ac. / Last Updated: August 03, 2017

Glutathione is a chemical constantly produced by our cells to maintain health, detoxify, and provide antioxidant activity, or clearing of free radicals. The highest levels of glutathione are found in the liver because the liver performs most of the detoxification and oxidant free radical clearing in our bodies, but glutathione by no means is confined to the liver, and is important to all cells in our bodies. Glutathione aids breakdown of oxidized fats that form a key part of atherosclerotic plaque, maintains the integrity of red blood cells, protects the white blood cells from damage, is integral to key enzymatic functions, helps break down molecules in the liver that are excreted as bile, and is crucial to our overall health. A deficiency of cellular production of glutathione is strongly linked to aging, neurodegenerative states, and a host of other diseases. Insulin resistance, a key factor in diabetes, obesity, and metabolic syndrome, has been linked to dysfunction in the glutathione metabolism. We see that the capacity for our bodies to produce the right amount of glutathione when needed is very important, and this glutathione metabolism is a key part of a healthy homeostasis. How to improve the glutathione metabolism in chronic disease states and during periods of physiological stress that challenge our health is an important question in health maintenance, the prevention of disease, and the treatment of many chronic diseases. Improved glutathione metabolism is not the complete cure for disease, but is an important part of a holistic integrated treatment strategy.

We cannot directly supplement glutathione, as we do with vitamins, because the ingested glutathione will be broken down by digestion into its key components, cysteine, glutamic acid, glycine and sulfur. A new glutathione supplement has been introduced on the market with a lipoprotein coating to delay this digestive breakdown, but we are waiting for scientific studies to confirm this as an effective delivery system. Taking glutathione supplement may also provide little benefit because glutathione is constantly produced in our cells and constantly converted from its inactive to its active form, and back again. The key to maintaining a healthy glutathione level and metabolism in our cells is to provide bioavailability of nutrients that help create glutathione and that help maintain balance, and when needed to take herbal medicines that are proven to stimulate increased glutathione when needed. Scientific studies (cited below in Additional Information) also show how specific acupuncture stimulations improve glutathione metabolism, and many studies show how herbal chemicals aid this important homeostatic mechanism as well. A comprehensive package of care, directed by a knowledgeable Licensed Acupuncturist and herbalist, or TCM physician, can dramatically help one maintain this healthy detox and antioxidant metabolism with just short courses of acupuncture and herbal formulas, and longer courses of essential nutrient medicines, taken periodically.

To maintain healthy cells and prevent disease and cancer, continuous chemical activity must occur to maintain the right chemical levels of glutathione and related metabolites, and a homeostatic balance, or stability, must be maintained. With different disease states and metabolisms the need and production of glutathione varies considerably, and to truly utilize glutathione metabolism in medical treatment and individualized and thoughtful holistic assessment and treatment protocol is needed. The common human response to such complex physiological problems is to look for the "silver bullet" and believe that some simple miracle product will restore glutathione and cure a disease, but this is a mistake. Physicians and patients need to take a more holistic and individualized approach to glutathione restorative medicine and see this as part of a more holistic integrative treatment protocol.

Homeostasis is the key to disease prevention and a holistic health regimen is the key to helping your body maintain proper homeostasis. One example of this homeostatic balance is acid and alkaline balance, which we call pH, and when pH in our cells and fluids is too acid or alkaline, our body chemistry, especially activity of protein enzymes that control rates of chemical conversions, becomes dysfunctional. This pH is the hydrogen ion concentration, which is the key factor in the bioavailability of free electrons, or biochemical energy. After this homeostatic balance is disrupted, disease mechanisms occur, and finally, symptoms are noticed. As symptoms are noticed, we want a quick fix to such problems as chronic fatigue, insomnia, pain, indigestion, constipation, etc. What we need to focus on is the more complex problem of maintaining homeostatic balance to get at the root cause of these symptoms. The glutathione metabolism is one of the most important aspects of our homeostatic balance, and gaining an understanding of this metabolism, taking the right foods, nutrient supplements, and herbs coud be the difference between a healthy or unhealthy future. Just as our cells work constantly to maintain balance, we must also participate consciously in this activity in the increasingly unhealthy environment that we have created for ourselves.

Glutathione Homeostasis and Traditional Chinese Medicine (CIM/TCM)

Balance in our metabolism is called homeostasis in modern times, although the Daoist scientist philosophers who formulated the theories of what we call Traditional Chinese Medicine would call it the balance between Yin and Yang. Yin and yang signify fluid and changing states that must always remain in balance to maintain health. Yin may turn into yang and vice versa, but the balance must always be maintained. The term homeostasis comes from the Greek words homois and histemi, meaning to be the same and constant, or in equilibrium, dynamically stable and balanced. It was a term coined by a famed Harvard physiologist, Walter Bradford Cannon, in 1932, to better describe this ancient concept. Homeostasis describes a holistic or quantum state where constancy must be maintained with a complex variety of mechanisms. Cannon wrote that the regulating system that determines the homeostatic state consists of a number of cooperating mechanisms acting simultaneously or successively. When these cooperating mechanisms experience imbalance or dysfunction, a healthy physiology is not maintained, and disease occurs. Often, to speed recovery from a disease or syndrome we first need to restore this homeostatic balance.

The glutathione metabolism is a very important system that must be maintained in this homeostasis, and must be maintained by providing the ability of the cooperating chemical mechanisms. We can't just take glutathione pills and be healthy. We must look at a number of metabolic parameters and give our bodies a chance to restore balance. If there are deficiencies in the glutathione metabolism, we must supply, or make bioavailable to our metabolism all of the essential nutrients. If there are excesses in the biological mechanisms, we must decrease them. These excesses could be excess oxidant stress, excess demand for essential nutrients, or excess acidity in the body. Cannon wrote that our homeostasis does not occur by chance, but is the result of self-government in our bodies, and to restore health and homeostasis we must give our bodies the ingredients and stimulation to allow it to restore proper self-government. The combination of acupuncture stimulation, nutrient and herbal medicine can provide the means of glutathione restoration. Modern medicine is largely based on allopathic treatment, meaning that we try to stop disease mechanisms by introducing something outside of what is physiologically normal to control symptoms. Traditional Chinese Medicine and Complementary and Integrative Medicine (CIM/TCM) seeks largely to restore homeostasis, and restoration of glutathione homeostasis is very important. The history of medicine has long involved a debate concerning the importance of the allopathic approach over over the holistic restorative approach, and unfortunately, we still seem to have difficulty in recognizing the importance of both.

Restoration of homeostasis could dramatically improve outcomes in allopathic medicine, and restoring a healthy glutathione metabolism is one of the key considerations. Glutathione is found throughout our bodies, but is especially important in our liver. It exists in two forms, reduced and oxidized, that must maintain balance, and as glutathione continually transforms proteins within the cytoplasm of our cells to cysteines as we need them, the oxidized form of glutathione is created and quickly reduced. The ratio of reduced glutathione to oxidized glutathione within our cells is used as a measurement of cellular toxicity. Glutathione metabolism almost defines antioxidant activity and detoxification to physiologists. In cells that are exposed to high levels of oxidative stress, up to 10 percent of the energy consumption, in the form of glucose, may be consumed by the glutathione reductase pathway. If this metabolism is not functioning properly the cell membrane, and the cell, will be destroyed, which is called lysis. When this happens to red blood cells excessively, we experience anemia. Glutathione dysfunction can lead to many disease states.

Scientists at the University of Rochester School of Medicine, Department of Environmental Medicine, wrote in 2009 that: "disturbances in glutathione homeostasis are implicated in the etiology and/or progression of a number of human diseases, including cancer, diseases of aging, cystic fibrosis, and cardiovascular, inflammatory, immune, metabolic, and neurodegenerative diseases."

Imbalances in the ratio between oxidative and reduced glutathione manifest largely as increased susceptibility to oxidative stress, and this is thought to be the main cause of diseases such as cancer, Parkinson's disease, Alzheimer's disease, and most of the chronic diseases that we worry about. When this fluid dynamic of glutathione states is deficient, antioxidant capacity in or cells is decreased, and when the glutathione ratio is in excess, the increased resistance to oxidative stress may unnaturally preserve the cell when it is cancerous, or suffering excess mutations. Recent research has shown that patients suffering neurodegenerative disease, such as Alzheimer's, are significantly less likely to get cancer, and this is because the glutathione imbalance that is protective against cancer with excess activity in some cells of the body is creating deficiency in others. Excess is destroying cancer cells, while deficiency is causing neurodegeneration. This is one mechanism that is believed to also cause resistance to chemotherapy. We see that preservation of glutathione bioavailability and balance is extremely important to our health. We cannot take an allopathic approach of inhibiting glutathione metabolism, for surely, the consequences will be devastating. We must learn how to restore glutathione metabolic balance is we are to truly restore healthy mechanisms. Fortunately, the treatments in TCM, namely acupuncture stimulation and herbal medicine, are largely shown to be modulating in their mechanisms, stimulating the body and supplying a group of chemicals evolved in the plant organism that helps the human organism work better. Many specific herbal chemicals are shown to increase glutathione capacity when the study animal has a disease state involving decreased glutathione capacity, but not to increase glutathione in a healthy control animal.

Helping the body to maintain a sufficient supply of glutathione, or glutathione bioavailability, is very important to our health. Glutathione is built on three amino acid peptides, glutamic acid, cysteine and glycine, and healthy protein digestion and assimilation is thus important to this glutathione bioavailabilty. Today, modern processed foods have created difficulties for many in digesting protein complexes, called gluten, and the response has been to avoid gluten, but little attention to restoration of a healthy functional capacity to digest these sticky protein complexes has been seen. Avoidance of healthy protein rich foods is not the ideal solution. In the glutathione metabolism, the protein amino acid cysteine is most important, and the oxidized, or reduced, glutathione is formed by a disulfide bridge between the cysteine residues of two glutathione molecules, protecting red blood cells from oxidation and destruction, and preventing sensitivity to oxidant drugs, especially acetaminophen. N-acetyl cysteine has been shown to be a valuable nutrient supplement to aid gut membrane health and function, and to aid glutathione metabolism. Sulfur rich foods include many fresh vegetables and fruits, especially onions, shallots, garlic, leeks, and brassicas, or cabbage, broccoli (rapini), Brussel sprouts and bok choy. Foods with plant-based protein are also a good source of sulfur, such as legumes, nuts (cashews) and whole grains, and the amino acids cysteine and methionine are are main sulfur-based amino acids in these foods. The supplement methylselenocysteine can also be valuable to supply these nutrients, and provides additional detox and support for the thyroid system. Eggs are also a rich source of sulfur, as well as parsnip, horseradish, black pepper corns, spinach, and the herbs butterbur, nettle, Sang bai pi (mulberry), and Qian hu. Both the diet and herbal and nutrient medicines are needed to create glutathione bioavailability.

How do we maintain glutathione balance?

Restoring or maintaining glutathione balance has been the subject of many studies for decades. The U.S. government's National Institutes of Health (NIH) maintains a partial list of medical studies that have been published, called PubMed, and lists 119,770 studies related to glutathione at present. After decades of research and many attempts to create allopathic pharmaceuticals to manipulate glutathione levels, there has been no success whatsoever, despite the obvious importance. Naturopathy has also failed to find a simple means of supplementation with dietary chemicals. At present, we have various combinations of essential nutrient supplements and herbs that are widely prescribed, even by medical doctors, to indirectly help the body maintain glutathione metabolism. What we are overlooking is that such an integral and complex metabolic mechanism in our body needs a holistic and thorough approach to restore. Just as calcium metabolism, which is perhaps the most regulated and complex metabolic process in our body, is not restored by simply taking calcium pills, glutathione metabolism is also not restored with simplistic approaches. Simply taking L-glutathione, or even the amino acids from which it is made, cysteine, glutamic acid and glycine, has not consistently resulted in increased cellular glutathione metabolism. Providing the raw materials for the glutathione metabolism, as well as herbal chemicals that are proven to potentially increase the glutathione activity is the ticket for success. While this protocol is more complicated than we like, the results will be appreciated in the long run, as the glutathione metabolism is very important to our cellular health.

Supplementation with liquid sublingual B12, 5MTHF (folic acid), P5P (Vitamin B6), N-acetyl-cysteine, zinc monomethionine, and methylselenocysteine (selenium) are recommended to insure improved glutathione metabolism. In additions, a number of herbs or herbal chemicals are proven to insure increased glutathione activity as well, including milk thistle, resveratrol, Wu wei zi (Schisandra berry), European olive tincture, Huang qin, Hu huang lian, Zi cao, Zhi cao, and many others. Common Chinese herbs that will improve the glutathione deficiency with liver dysfunction include Chai hu (bupleurum) and Yu jin (curcuma), as well as E zhu (curcuma) and Dan shen (salvia miltiorrhiza). The explanation and proof of this is provided below, and in the section entitled Additional Information with links to research at the end of the article. As more and more studies of this glutathione metabolism are being researched, we are finding that more and more Chinese herbs are able to improve glutathione capacity in disease states. To insure that the glutathione metabolism is working optimally, it is best to periodically supplement with these nutrients and herbs. Of course, a diet rich in these nutrients would be the best option, and this article also suggests foods rich in these nutrients. If liver toxicity is suspected, or liver dysfunction or injury due to disease or adverse effects of medications, a prolonged course of 8 weeks of these herbal and nutrient medicines is advisable, as demonstrated with scientific studies cited below. In professional Chinese Herbal Medicine, or TCM, the Licensed Acupuncturist and herbalist routinely uses these herbs in herbal formulas that have been used for centuries to improve liver and cardiovascular health. With these scientific studies, we now see proof of the efficacy of this approach. Holistic medicine and CIM/TCM provide an array of benefits whenever it is utilized, and this is largely overlooked in an age where we want a simple binary explanation to all treatments. Even when a symptom is not immediately relieved by an herbal medicine, or acupuncture stimulation, the array of proven benefits are still there, and should not be discounted.

How these herbal chemicals work to induce improved glutathione metabolism has also been the subject of extensive research. For example, one herb used extensively in Chinese herbal medicine (CHM) that is a potent clearer of infections, is Andrographis paniculata, called Chuan xin lian in China, and this herb is widely used to treat liver toxicity and hepatitis. The herb has potent anti-viral and anti-inflammatory effects. The main active chemical component in Chuan xin lian is Andrographolide, which is shown to enhance the expression of an enzyme the controls the rate of glutathione production, glutathione S-transferase. Studies at Chung Shan Medical University in Taichung, Taiwan, in 2010, found that this herbal chemical works via activation of the PI3K/Akt, phosphorylation of c-jun, nuclear accumulation of AP-1, and subsequent binding to the response element in the gene promoter region of the enzyme that controls the rate of glutathione expression. PI3K/Akt is a cellular signalling pathway important also in the regulation of cell programmed death (apoptosis), and hence prevention of cell mutation and cancer. C-jun and C-fos are regulatory proteins that control cell proliferation, and are part of the activator protein AP-1, which regulates gene expression in response to a variety of stimuli, including inflammatory cytokines, growth factors, bacterial and viral infections, and stress. We see from such detailed study in China that this herbal chemical has evolved within a natural framework to stimulate processes within our cells that act to protect us from harm and keep our cells healthy despite a variety of environmental threats. This one herb, Chuan xin lian, is proven to help us clear a variety of infections, clear toxins, and even prevent cancer. Scientific study in the laboratory confirms what we already observed empirically for hundreds of years in China. To see this study, click here: The time for doubting the efficacy of Chinese herbal medicine is nearly over, and this is just one example of many that are researched and proven to provide amazing health benefits in a holistic treatment protocol.

One aspect of glutathione imbalance is high homocysteine, which is now known as a marker for a variety of serious chronic diseases, including osteoporosis, atherosclerosis, cardiovascular disease, chronic kidney failure, dementia, Behcet's disease, and more. At first, scientists looked to correct high homocysteine to control the disease, and thought that the high levels must mean that it is a direct mediator in the disease. After lowering the homocysteine levels did not correct the disease, and with high homocysteine observed as an accurate marker of so many diseases, we now consider it a marker of disease activity, and not a mediator.

We still fail to fully grasp that high homocysteine is a marker of metabolic imbalance that relates to an unhealthy state, and a homeostatic dysfunction. When homocysteine is not converted to other metabolites in the body, high circulating levels result. Glutathione metabolism in the cell, the action of glutathione in clearing oxidants, results in creation of cysteine. Maintenance of glutathione homeostasis requires constant ability to convert glutathione to cysteine or methionine. One of the cysteine metabolites in this process is homocysteine. Therefore, high circulating homocysteine is a disease marker that probably signifies a dysfunction of glutathione metabolism. The most significant research on high homocysteine and nutritional medicine found that supplementation with Vitamin B12 (sublingual or injected preferrably), folic acid (active form = 5MTHF), and Vitamin B6 (active form = P5P), had significant effects in most patients to reduce high homocysteine by improving the glutathione cysteine metabolism. To insure adequate glutathione homeostasis, you may want to add other important nutrients as well, and possibly utilize herbs proven to increase the glutathione metabolism.

Cysteine levels in our body are intricately tied to glutathione bioavailability. Cysteine is not an essential amino acid, meaning that levels in the body are determined by cellular production, not dietary intake. Nevertheless, supplementation with cysteine has been shown to have an affect on glutathione metabolism. One study showed that white blood cells constantly produced glutathione, and that availability of cysteine enhanced glutathione production in a dose-dependant manner, but only when these lymphocytes had sufficient lipopolysaccharides (LPS) available. Lipopolysaccharides make up the outer membranes of gram-negative bacteria, and so, the study showed that glutathione production in the white blood cells increased as needed, in response to low-grade bacterial infection in the body, but that cysteine availability was important to counter these inflammatory mechanisms in disease. Lipooligosaccharides, a low molecular version of LPS endotoxins, are linked to many autoimmune diseases as well. Deficient production of glutathione linked to deficiency of N-acetyl cysteine is now known to be important in the pathology of a variety of diseases, including Parkinsonism and other neurodegenerative diseases, schizophrenia, leukodystrophy, AIDS, and various autoimmune diseases. Various forms of cysteine are effective as supplements, including selenocysteine, N-acetylcysteine (NAC), methylselenocysteine, and L-cysteine. Selenocysteine combines selenium with cysteine, and is found in various enzymes, including glutathione peroxidases, making this supplement especially beneficial to glutathione antioxidant activity. N-acetylcysteine (NAC) is a supplement that aids glutathione detoxification function, liver health, and also benefits the mucus membrane of the gastrointestinal tract. It is also a potent antioxidant. NAC is now available as a pill, powder, or aerosol spray.

Methionine: Cysteine can be synthesized by our cells if there is a sufficient quantity of methionine available. Methionine is an essential amino acid, meaning that we must have a sufficient supply in our diet. Thus, supplementation with methionine could provide for improved glutathione metabolism. Consuming foods with methionine may also be helpful, and these include sesame seeds, sunflower seeds (if fresh), brazil nuts, pistachios, fish, caraway, fennel, coriander, and cumin seeds, spinach, pumpkin seeds, taro, soy, bean sprouts, oats, barley, barleygrass, wheat, watercress, asparagus, chives, beans and lentils. Various forms of methionine are potentially helpful, including SAMe (S-adenosyl-methionine), zinc methionine (Opti-Zinc), . There are many metabolic pathways in our body that convert amino acids. One pathway, the synthesis of methionine, involves cysteine to homocysteine to methionine. We see that there are metabolic cycles involved, where cysteine is created when there is sufficient methionine, and methionine is created when there is sufficient cysteine. While we cannot control for all of the necessary metabolic needs of this metabolism, a holistic approach, where the key nutrient chemicals are taken in combination, general health is improved, and metabolic stress is reduced, will have positive effects in restoring glutathione capacity.

Pantothenic acid: a less direct nutritional supplement, pantothenic acid, or Vitamin B5, has been found in studies to promote glutathione synthesis or prevent its degradation when oxidative stress threatens our cells (Biofactors 2003;61-73; L. Wojtczak, V.S. Slyshenkov). B5 is an essential cofactor in production of cellular energy (coenzyme A and ATP), and has been proven to aid liver function and lower triglycerides, promote tissue healing, protect white blood cells from oxidative damage, and aid hormonal metabolism in the liver as well. Alpha lipoic acid (ALA) has also been found to indirectly aid glutathione metabolism, via increased cysteine uptake when the reduced form of alpha lipoic acid, alpha-dihydrolipoic acid (DHLA), is created. Although this effect is transitory, supplementation with ALA could prove beneficial when increased oxidant stress is experienced.

Studies have found that a deficiency of selenium may account for a deficiency in the glutathione metabolism. Selenium is a key component of the enzyme glutathione peroxidase, which regulates a key antioxidant and detox mechanism in the cells. Animal studies showed that taking a selenium supplement increased this glutathione enzyme activity 47% (see study cited below). A type of selenium supplement called methylselenocysteine is more useful, providing both selenium and cysteine, and acting in the methionine pathway. Sulfur containing amino acids are also integral to this enzymatic process, namely cysteine and methionine, and studies have found that concurrent supplementation with these amino acids and selenium achieves a higher efficiency in the glutathione metabolism. Studies have long confirmed that adequate selenium in the body will divert methionine to the glutathione pathway. While taking just one of the component supplements may provide an improved glutathione metabolism, omission of a key nutrient chemical, if it is deficient in the body, will insure indadequate glutathione activity.

Alpha-Lipoic Acid (ALA) is an antioxidant that has been shown to be capable of regenerating glutathione and other antioxidants, and thus ALA and R-Lipoic Acid (RLA) have been much studied in disease prevention and treatment. A 2015 study at the Tongji Medical College School of Public Health, and Huazhong University of Science and Technology, in Wuhan, China, found that ALA significantly attenuated the toxicity of human liver cells exposed to cadmium, a now common heavy metal contaminant. ALA increased the activity of rate limiting enzymes in the glutathione metabolism, and attenuated the level of cadmium in fat cells, and was thus shown to be an important part of the holistic treatment to prevent and treat liver toxicity and increase glutathione bioavailability (PMID: 26365678).

Various herbs and herbal chemicals have also been found to increase glutathione synthesis. Resveratrol, an active chemical found in various herbs and foods, but extracted from the Chinese herb Hu zhang, or Polygonum cuspidatum, in all supplement pills, has been found to induce glutathione synthesis. This herb was also found to be effective in chelation of copper accumulation, a common heavy metal toxin in certain forms, and to reduce tumor size in a dose-dependant manner. In the past, copper toxicity was considered only in the very rare inherited Wilson's Disease, where copper cannot be efficiently eliminated by the liver, but in 2013, scientists at the University of Rochester Medical Center in New York, U.S.A. found that even in those without this disorder, that copper accumulation in the brain disrupted the natural removal of amyloid beta plague that is a hallmark of Alzheimer's disease, as well as stimulating increased production of amyloid beta. Obviously, failure to clear these common heavy metal ions is a prevalent problem, especially as we age, and Resveratrol could provide great aid to both copper clearance and glutathione detoxification. More and more research continues to uncover evidence that Chinese herbs increase glutathione synthesis when our bodies' cells need increased cellular protection and detoxification. The herb Picroria kurroa (Picrorhiza kurrosa, or Hu huang lian) contains an active ingredient called apocynin which was found to significantly increase glutathione levels in epithelial cells in just 24 hours. Standard dosage increased glutathione production in epithelial cells exposed to oxidative stress by up to 111%. Glutathione enzyme activity was also significantly increased, and the herb's active ingredient inhibited the production of harmful superoxides and hydrogen peroxides that create excess oxidative stress and cellular damage. Not only anti-inflammatory herbs, but adaptogenic herbs have also been proven to aid glutathione metabolism. Ashwaganda, Withania somnifera, was found to increase glutathione peroxidase, catalase and superoxide dismutase in brain cells of study animals, exerting significant neuroprotective antioxidant effects and aiding glutathione activity (Russo et al, Univ. of Catania, Italy).

Some of the more commonly used herbs proven to promote glutathione production include milk thistle, European olive leaf extract, and Schisandra chinensis berry (Wu wei zi), and a variety of supplement formulas are now offered with these herbs combined with key nutrient supplements. As more scientific research continues, we will see that a variety of Chinese herbs benefit the health by improving glutathione metabolism and production, as well as improving liver function and decreasing oxidative stress. The many benefits of Chinese herbal formulas certainly exceed the immediate symptom relief that is noticed, and the smart patient understands that this ancient holistic medicine is providing improved health by restoring homeostasis.

Various diseases may inhibit healthy glutathione metabolism and function

Diabetes, or metabolic syndrome, is a disease that can lead to many devastating chronic health problems. In chronic states of diabetes, circulatory disorders and degeneration can lead to peripheral neuropathy, macular degeneration of the eyes, poor circulation and gangrene, and other disorders. The risk of stroke and heart attack increases dramatically. Insulin is a hormone that regulates blood sugar and insulin dysfunction is tied to diabetes and metabolic sydrome. Scientific studies have also found that glutathione metabolism is inhibited in diabetes, especially the functions of key glutathione enzymes that control glutathione levels, glutamuylcysteine synthetase and glutathione reductase. Insulin is a hormone that mediates the functions of these enzymes, and glutathione metabolism. In the study, insulin effects were blocked when levels of adrenal hormones were too high. Not only poor insulin production, but insulin resistance, and adrenal stress all contributed to dysfunction of cellular glutathione production.

Neurodegenerative diseases as well as acute neuronal damage from stroke are associated with oxidative cell damage that inhibits cellular glutathione metabolism. There are many chronic neurodegenerative diseases, the most well known being Alzheimer's and Parkinson's, but a large percentage of the population is afflicted with central nervous system neurodegeneration, and such problems as attention deficit and hyperactivity disorder and glaucoma are examples of how problematic neurodegeneration is. Acute damage from cardiovascular disease is also more prevalent than we imagine, with transient ischemic attacks, or TIAs, often occurring unnoticed or unreported. In these states, scientific study has shown that inibition of glutathione metabolism, both cellular production and deficient glutathione enzyme activity, contribute greatly to CNS damage. The most abundant neuroexciting neurotransmitter is the glutamate molecule, and with neurodegeneration and acute damage, excess glutamate release can cause neuronal cell death through both increased calcium influx and toxicity, and inhibition of clearing calcium ions from the cells. When this happens, there is increased oxidative stress, and increased need for effective oxidative clearing. The glutathione metabolism is one of our chief lines of defense and neuroprotection, yet the mechanisms that create the glutamate excess also appear to inhibit glutathione metabolism.

These studies, and many other studies of disease mechanisms adversely affecting the glutathione system, show that to effectively restore health glutathione metabolism, underlying disease states must be evaluated, and when appropriate, treated effectively. While allopathic medications may keep these disease states under control symptom-wise, they will not address the whole picture of functional health. Complementary and Integrative Medicine provides a holistic approach to help restore healthy metabolic function in disease states. In the case of metabolic syndrome, a holistic approach may analyze hormonal balance and utilize a combination of therapeutic tools to restore both the insulin metabolism and adrenal health. This type of integrative care, coupled with the taking of quality nutrient supplements and herbal chemicals, provides a more thorough and individualized approach to restoring glutathione function and preventing a host of diseases.

Besides the nutrient supplements that help our bodies to have increased bioavailability of glutathione, such as methionines, N-acetyl-cysteine, B12, and folic acid, there are a number of herbs that have been proven in research to be able to potentiate glutathione metabolism or to alleviate the stress on the glutathione mechanisms. One example is Wogonin, from the Chinese herb Scutellaria baicalensis, or Huang qin, which exhibits neuroprotective action in cultured brain cortical cells by inhibiting excess excitotoxicity and oxidative stress damage, showing potent antioxidant activity as well (J Cho, HK Lee, European Journal of Pharmacology 2004;485:105-110). Another interesting subject of research concerns the neuroprotective and antixodant effects of hormones and neurotransmitters. Studies have shown that estrogens, melatonin, and Vitamin E alpha tocopherol, all exhibit antioxidant and neuroprotective effects, as well as protecting against depression, anxiety, insomnia, and emotional agitation, by protecting against kainic acid excess, which inhibits the GABA neurotransmitter that helps regulate our mood. Holistic balancing therapy with bioidentical hormones, 5HTP, and various herbs and supplements can reduce the biological stresses that inhibit glutathione antioxidant clearing and detoxification. The benefits to this type of comprehensive therapy are many. Of course, a knowledgeable Complementary Medicine physician, or Licensed Acupuncturist, who spends the time to properly evaluate and treat comprehensively, is very important.

Synthetic chemicals, including medications, can stress the capacity of our liver detoxification metabolism, and upset glutathione balance, just as environmental pollutants and toxins can

As stated, synthetic medications, and the products created from the catabolism of synthetic medications, are treated as toxins in the liver and intestinal tract. The rate of chemical breakdown in the liver, or detox, usually determines the levels of prescription drugs in the body. When liver detoxification is not efficient, these levels of circulating synthetic drugs may be altered, resulting in overdosage and potential harm. Many side effects of medication occur well after starting the medication, and are the result of slow increases in circulating levels of the chemicals because of inefficient breakdown, or catabolism, of the drug. There are many published cautions or contraindications in drug combination, and these are mainly addressing the drugs that use the same metabolic methods of breaking down the drugs in the liver. Too often, these contraindications and warnings are ignored. The family of liver enzymes referred to as P450 are the most well known metabolic factors that regulate the rate of drug catabolism. Dangerous drug interactions may occur when one drug inhibits or induces a P450 enzyme activity and slows or speeds the breakdown of other drugs in the liver, resulting in altered levels of circulating dosage. By taking a number of drugs that utilize the same P450 enzymes, the chance that the circulating levels will be altered over time increases. Sometimes, the stress that this creates on the liver contributes to unhealthy liver function.

The most well known drug that causes deficiency of the glutathione metabolism and liver damage is acetaminophen, a pain reliever that is commonly used and overused. While acetaminophen is most well known as an over the counter common pain reliever, i.e. Tylenol, Midol, Excedrin, et al, what people do not realize is that this drug is added to hundreds of medications, making excess intake of acetaminophen a serious health problem. This practice has become so widespread that the FDA had to start a series of steps to decrease acetaminophen usage in 2009 by the pharmaceutical industry. Acetaminophen is found in almost all prescription pain medications, such as narcotics and synthetic narcotics, as an additive, and is also found in a variety of decongestants, allergy medications, cough medicines, cold and flu medicines, headache medicines, etc. If a person is afflicted with a variety of common health problems they are probably overdosing on acetaminophen, and causing much stress on the glutathione metabolism. A study in 2015, at LI'an Jiaotong University, in China, showed that a chemical in a number of common Chinese herbs, luteolin, significantly relieves acetaminophen liver damage and stress in laboratory animals, showing reductions in glutathione depletion and a host of other benefits, including decreased oxidant stress, toxic malondialdehyde, excess AST liver enzyme, and inflammatory cytokines TNF-alpha and IL-6 (PMID: 26002582). Luteolin is found in the Chinese herbs He zi (Terminalia chebula), Jin yin hua (Lonicera japonica), Ju hua (Chrysanthemum morifolium), Jin gu cao (Ajuga decumbens), and Lu cao (Humulus scandens), and represents just one of the effective flavonoids found in Chinese herbs that alleviate glutathione depletion. A look at the research at the end of this article is sure to convince anyone that standard treatment protocols in TCM care will improve the glutathione metabolism and contribute to disease resolution and prevention.

Addressing liver health is of prime importance in detoxification. It is best to decrease the stress on the liver by decreasing the amount of chemicals in the body, by adopting a more natural diet and home environment, and by decreasing medication dependency whenever possible. Most drugs are immediately broken down by a certain percentage in the liver (over 4-12 hours), although some directly deposit in the body tissues, such as muscle, fat and bone, and may accumulate, just as other chemical toxins do. The rate of immediate breakdown, or catabolism, is called the half-life, implying that half of the drug is broken down into metabolites in a short period of time. This determines the time between dosage of the drug. The more prescription drugs that are taken the more stress is placed upon the liver detoxification system, probably resulting in less efficiency in detoxifying unwanted chemicals or pollutants that we ingest by eating, drinking or breathing, as well as the other drug metabolites. When the liver is unable to clear toxins and chemicals efficiently, these environmental toxins and drug catabolites may circulate and deposit in the body tissues, often with fatty encapsulations to prevent contact with normal tissues. This type of tissue accumulation increases over time and eventually contributes to degeneration, disease and aging.

The rate, or efficiency, of toxin breakdown, or catabolism, in the liver is primarily determined by the enzyme metabolism. Enzymes are a class of molecules, mostly proteins, that regulate rates of metabolism and catabolism. When the liver is dysfunctional, the blood tests show that the liver enzyme transanimases are high in circulating blood. These are termed AST and ALT on your blood tests. High transanimases in circulation implies a problem with liver function, and/or high stress put upon the liver. Normal levels are exceeded in liver disease, but even levels in the high end of the normal range imply liver stress of a subclinical nature. Enzyme metabolism may be normal on the blood test, but the liver may still have problems affecting detoxification metabolism. If the liver tissues accumulate toxic metabolites, such as oxidant free radicals, the tissues may become inflamed and may harden (cirrhosis), and decrease efficiency of liver metabolism significantly. Therapy is directed toward clearing antioxidants and protein fragments, increasing circulation, and aiding the enzyme and glutathione metabolism in the liver. The degree of ill health of the liver is determined by the physician, who then prescribes the most tailored logical combination of herbs and supplements. Typically, a short course of herbal formula, with milk thistle, Vitamin B6, L-cysteine, L-glutamine, OptiZinc, alpha-lipoic acid, and N-acetylcysteine optimize the goals above. Proteolytic enzymes may also benefit tissue clearance in the liver. This course of nutrients optimizes various antioxdant pathways and provides the best bioavailability of glutathione, the key antioxidant.

Studies have shown that common environmental toxins, or pollutant chemicals, accumulate in the body tissues. Even a healthy person with a good diet, in an urban area, accumulates a large amount of toxic chemicals in the tissues over time. The older we are, the more difficult this detox becomes. Since true detox of our tissues is a complicated process, repeated, or habitual, detoxification help is the only real way to clear the body of toxins. Promotion of liver and intestinal health, as well as the avoidance of as many chemicals as possible is also essential, and should become a lifelong process. This involves a diet of organic foods, unpolluted water, and breathing of unpolluted air whenever possible, as well as avoidance of household chemicals such as chemical cleaning products. When this entire regimen is adopted, maximum detox is achieved. Since elimination by the GI tract is one way of detoxifying, fasting may also be a valuable aid, if you can tolerate fasting. What is most important, once again, is a healthy functioning GI and liver system. You may want to correct your digestive problems, and improve liver health with a course of treatment before adopting a detox regimen. This will insure better results. Herbal therapies may also provide stronger intestinal detoxification. Herbs with a high content of tannic acids can precipitate toxic substances in the intestinal lumen, converting them to insoluble substances, so that a high fiber diet or fast can eliminate them. Wu bei zi is an herb used in China for this purpose.

Once again, the medical advice presented is more complicated than we would wish for. The idea that the human physiology is simple, and correcting problems with our health can be achieved with the magic pill or simple routine, is a fairy tale that we all buy into in a consumer society. It's easier to advertise simple solutions, and so this is what we repeatedly hear. Reality is more complicated, but can be simplified by putting the process into the hands of a professional and following the professional advice. Each year, more and more scientific study demonstrates the efficacy of a wide range of herbal and nutrient medicines, as well as acupuncture, in the aid of our glutathione and antioxidant metabolism. With a wide range of proven therapies, the Licensed Acupuncturist and herbalist can choose an individualized therapy for each patient to achieve the best results safely and efficiently.

Information Resources: Additional Information and Links to Scientific Studies

  1. In 2009, scientists at the University of Rochester School of Medicine, in Rochester, New York, wrote of glutathiione dysfunction and the many disease implications:
  2. Scientists at Texas A&M Univesity explained the basics of glutathione metabolic maintenance and its importance to health in 2004:
  3. A 2013 paper by experts at St. Jude Children's Hospital, Department of Developmental Neurobiology, in Memphis, Tennessee, U.S.A. notes that it has been well established that glutathione capacity in reducing oxidative stress in neural cells is the key to preventing or reversing Parkinson's disease:
  4. In 2009, scientists as Osaka University, in Japan, published a study in AJP-Endocrinology, that detailed how dysregulated glutathione metabolism plays a key role in insulin resistance and obesity:
  5. In 2009, researchers at the Harvard Medical School in Boston, Massachusetts, found that high homocysteine levels, part of the glutathione imbalance, was highly linked to increased risk of hip fracture:
  6. A 2008 study of the metabolic effects of electroacupuncture revealed that stimulation at a single point, ST36 zusanli, in laboratory animals, produced significant reduction of oxidative stress via a number of pathways, including enhanced glutathione metabolism. The study was conducted at Kyunghhee University College of Oriental Medicine and Korea University in Seoul, South Korea, and published in Molecules and Cells, Vol.25 (No.2);178-183:
  7. A 2014 study in China found that electroacupuncture stimulation at 3 commonly used points, DU20, SP6 and LV3, of alternating 2/80 Hz, resulted in restoration of anitoxidant and detoxifying markers super-oxide dismutase (SOD) and glutathione peroxidase (GSH-Px), as well as a decrease in the key marker for cell toxicity, malaondiadelhyde (MDA), in the substantia nigra and dopaminergic neurons of the brain, in studies of laboratory animals:
  8. A 2013 study at Peking University, in Beijing, China, found that electroacupuncture at just 2 common points, ST36 and SP6, at 100 Hz, significantly increased glutathione activity and super-oxide dismutase antioxidant (SOD) in the substantia nigra in the brain:
  9. A 2014 randomized controlled study in China found that electroacupuncture at the points DU20, SP6 and LV3 at the alternating frequency of 2/80 Hz, daily for 14 days, significantly increased glutathione and superoxide dismutase activity in the substantia nigra of laboratory animals with Parkinsonism, and cleared malondialdehyde toxicity, while improving the health of the neurons. In comparison, the medication Rotenone did not achieve these effects:
  10. A 2013 study at the Federal University of Ceara, Brazil, found that both acupuncture and electroacupuncture stimulation increased glutathione in tissues of the ovaries and increased malondialdehyde concentrations in the blood plasma, while decreasing myeloperoxidase activity (antioxidant need) for laboratory animals with induced inflammation by excessive estradiol stimulation:
  11. A 2011 study at Kansai University, Osaka, Japan, found that electroacupuncture and manual acupuncture both significantly increased glutathione levels in muscle tissue compared to controls, and that manual acupuncture, but not electroacupuncture, increased carnitine levels, in fatigued muscles. These markers are key indicators of muscle fatigue as well as markers for the disease in syndromes of muscle fatigue, such as autoimmune Dermatomyositis and Polymyositis:
  12. A 2015 randomized controlled study of the effects of acupuncture in an integrative treatment protocol for alcoholism, at Khon Kaen University, in Khon Kaen, Thailand, found that stimulation daily for just 14 days at one point, HT7, significantly decreased malondialdehyde toxicity, and acetylcholinesterase activity in the hippocampus, and enhanced glutathione metabolism and SOD antioxidant effects:
  13. A randomized controlled study at Yichun College, in China, found that acupuncture stimulation at the points ST36 and SP6 remarkably improved the glutathione metabolism and SOD antioxidant activity to clear malondialdehyde in laboratory animals with Chronic Fatigue Syndrome:
  14. A 2013 study at Daejeon University, South Korea, found that even common indirect moxibustion therapy in TCM significantly increased glutathione activity and reduced toxicity in blood plasma measured by malondialdehyde levels, relieving chronic fatigue:
  15. A 2007 study of melatonin at the Medical University of Lodze in Poland found that this supplement increases glutathione and antioxidant enzymes, neutralizes reactive oxidative free radicals, reduces proinflammatory cytokines, and increases total antioxidant capacity to effectively treat atherosclerosis:
  16. A 2008 study at the University of Rochester Medical Center in New York found that resveratrol induced glutathione synthesis. Resveratrol is a potent antioxidant, and in the body it stimulates genetic activation that results in increased glutathione production:
  17. A 1999 study at the Leiden University Medical Center in Leiden, Netherlands, and the University of Edinburgh, UK, showed that the Chinese herb Picroria kurroa (Picrorhiza kurrosa, or Hu huang lian) directly and significantly increases glutathione cellular synthesis and glutathione enzyme activity in epithelial cells:
  18. A study in 2010 of the glutathione boosting activity of a Chinese herbal constituent, shikonin, from the herb Lithospermum erythrorhizon, or Zi cao, decreased reactive oxidant free radicals, up-regulated superoxide dismutase, catalase and glutathione peroxidase activities and reduced reactive glutathione in brain cells, demonstating dramatic neuroprotective and antioxidant qualities in a stroke study:
  19. Another Chinese herb, Salvia plebeia, or Zhi cao, was shown also to elevated the levels of glutathione, glutathione peroxidase, and superoxide dismutase, as well as lowering high liver enzymes, and decreasing the inflammatory mediators TNF-alpha and Interleukin-1, to demonstrate dramatic effects treating hepatitis and other liver disease:
  20. A 2008 study at Taipei Medical University in Taipei, China, found that the herbal chemicals curcumin and saikosaponin, found in the herbs Jiang huang (turmeric) and Chai hu (bupleurum), as well as the curcuma herbs Yu jin and E zhu, reversed liver impairment of superoxide dismutase activity and increased glutathione activity in laboratory animals with induced liver toxicity or dysfunction. These herbs also lowered elevated liver enzymes, and decreased cholesterol and triglyceride levels:
  21. A 2015 study at China Agricultural University, in Beijing, China, found that the herbal chemical curcumin, now widely standardized in supplements, significantly alleviated glutathione depletion and super oxide dismutase in human liver cells, as well as providing cell protection against cancer mutation:
  22. A 2015 study at the Medical University of Sofia, in Sofia, Bulgaria, found that flavonoid chemicals in the Chinese herb Chai hu (Bupleurum L.) ameliorated glutathione stress, and significantly reduced levels of malondialdehyde and lactate dehydrogenase, 2 essential markers of cellular toxicity, in laboratory studies. These experts also found that these Bupleurum flavonoids worked synergistically with rutin and narcissin, 2 other chemicals in the Chinese herbal medicine:
  23. A 2007 study at the Hepatitis Institute affiliated with Capital University of Medical Sciences in Beijing, China, found that the herbal chemical salvianolic acid A, found in Dan shen (salvia miltiorrhiza), significantly increased glutathione and superoxide dismutase activity in laboratory animals with induced liver toxicity or dysfunction. Dan shen also decreased elevated liver enzymes and malondialdehyde concentration in the subjects livers:
  24. A 2014 study at Hong Kong University of Science and Technology, in China, found that beta-sitosterol from the Chinese herb Rou Cong Rong (Cistanche) significantly increased glutathione activity by upregulation of mitochondrial glutathione expression, proving cardioprotective effect:
  25. A 2015 study at China Medical University, in Beijing, China found that the main active chemical in the Chinese herb Trypterygium wilfordii, or Lei gong teng, much studied as a significant adjunct treatment for autoimmune disorders, called triptolide, also has been shown to hlep alleviate injury after an ischemic stroke, and this study showed that it could help protect against heart attack (myocaridal ischemia). The beneficial effects included upregulating the expression of glutathione and superoxide dismutase (antioxidant), as well as the inhibition of excess inflammatory cytokines such as TNF-alpha, IL-1beta, and IL-6. Such study of laboratory animals proves that Chinese herbal medicine provides significant varied benefits with both preventive and treatment applications:
  26. A 2016 study at the Guangzi University College of Animal Science and Technology found that the common herb Polygonum hydropiper, used in China and the United States (water pepper, thyme) traditionally to treat dysentery and gastroenteritis, pain, swelling and inflammation, and which contains quercetin, rutin, and other well studied herbal antioxidants, increases the levels of glutathione, superoxide dismutase, and decreased the inflammatory cytokine TNF-alpha, as well as the toxin malondialdehyde in laboratory animals with bacterial lipopolysaccharide induced inflammation:
  27. A 2015 study at the Xi'an Jiaotong University Health Science Center, in Xi'an, China, found that the Chinese herb Pueraria lobata, or Ge gen, commonly called kudzu, significantly elevates the glutathione capacity and the antioxidant capacity as measured by superoxide dismutase (SOD) in the cells of laboratory animals with induced Alzheimer's disease. The level of toxic malondialdehyde in the cells was reduced with use of Ge gen at sufficient dosage for 28 days, and memory and learning functions were improved:
  28. A study at Oregon State University in 1989 found that methionine helps divert selenium in the body to the glutathione pathway:
  29. As far back as 1983 we have found that selenium, cysteine and methionine are key components to the primary glutathione enzyme glutathione peroxidase, which is the primary intercellular antioxidant and detoxifier in the body:
  30. A 2015 paper by experts at the University of California in San Francisco (UCSF) and the San Francisco Veterans Affairs Medical Center, in the U.S. notes that the use of the nutrient supplement N-acetyl Cysteine (NAC) is now entering human clinical trials for its use as an integrated therapy for a variety of diseases linked to glutathione imbalance and dysfunction, including Parkinsonism and schizophrenia. These experts are conducting laboratory experiments to determine the effective dose for humans. Of course, what is overlooked in modern medicine is the variety of physiological circumstances and the need to take a more holistic approach, not achieve a one-size-fits-all standardized dosage:
  31. A 2015 study by UCSF and the Veterans Affairs Medical Center in San Francisco, California, U.S.A. and the Emory University School of Medicine, in Atlanta, Georgia, U.S.A. found that N-acetyl cysteine presents a viable adjunct integrative role as part of a more holistic treatment of Parkinson's disease by restoring glutathione balance in the CNS, and could be measured with cerebrospinal fluid samples to adjust dosage. Of course, a more comprehensive treatment utilizing an array of herbs, nutrient medicines and acupuncture could achieve the goal of glutathione restoration even more:
  32. An example of medication breakdown, or catabolism, in the liver, which produces even more harmful chemicals than the medication itself, is cited in this study of AZT catabolites:
  33. An example of the harmful effects of acetaminophen on the gluthathione metabolism and widespread potential harm, including such tissue problems as cataract formation, is shown in this 1996 study:
  34. A conservative but informative article from the American Heart Association explains some of the pharmacodynamics of prescription drugs and the effect on the liver, with drug-drug contraindications and explanation of ill effects on the liver metabolism with statin drugs to lower cholesterol:
  35. A 2000 FDA labeling approval for a synthetic estradiol oral contraceptive reveals that concentrations of drugs in the body vary considerable from person to person depending on the individual health of the liver metabolism and competition for detox pathways:
  36. A 2008 study published in the European Journa of Cancer Prevention showed that a percentage of the population is born with genetic polymorphisms, or tendency to express misshapen protein enzymes, related to alleles expressing P450, glutathione S-transferase and N-acetyl transferase. In the population with deficient expression of both the glutathione and acetyl transferase enzymes, risk of acquiring acute myeloid leukemia, or bone marrow cancer, increased nearly 12%: Another study in 2000 found a significant relationship between deficient expression of P450 and glutathione transferase enzymes and esophageal cancers: These studies were a follow-up to a 1997 study of glutathione deficiency genotypes and the relationship to cancer susceptibility by the University of Pennsylvania School of Medicine: