Article Summary:
- Protecting the health of the liver is essential to long-term wellbeing
- Research suggests that using glutathione and milk thistle in concert can enhance liver health by protecting against oxidative stress, improving cellular function, and supporting the detoxification process
- Selecting high-quality supplements designed to maximize therapeutic benefit is essential to ensuring the best results
Working day and night to metabolize chemicals of all sorts, the liver is constantly in action. Yet livers are not infallible, nor are they invulnerable. As people age, their livers accumulate damage which prevents them from operating at their full capacity. Consumption of alcohol and other toxins exacerbate the rate at which this damage occurs, leaving the body with a slower metabolism and a reduced ability to detoxify. With a weaker liver, the body is exposed to toxins for longer and in a wider array of tissues, causing dysfunctions ranging from jaundice to cancer. Keeping the liver in good condition should, therefore, be near the top of patients’ healthcare priorities.
To keep the liver in good shape, many patients turn to detoxification regimens. Detox regimens aim to purge the liver of toxins which allegedly accumulate there, thereby improving its function. While the scientific basis behind most detox regimens is more fable than fact, there are still a number of practices which patients can use in specific situations to improve their liver’s ability to combat toxins.
The most effective detox regimens contain compounds which behave synergistically with regard to the liver’s function. In other words, these detox regimens have compounds which are more effective when administered together than one would expect. Patients seeking one of these especially effective regimens have recently discovered a powerful new combination: glutathione and milk thistle extract. Milk thistle is a bioactive herb which has long been associated with liver health; in contrast, glutathione is a chemical naturally created by the body that is highly concentrated in liver cells. Both chemicals are safe, natural, and effective means of protecting the liver from damage. While a natural liver detox using glutathione and milk thistle will not reverse any accumulated damage that occurred prior, patients who opt to try the regimen will reliably experience its protective and liver-enhancing effects.
What Is Glutathione?
Glutathione (GSH) is a chemical created by the body to protect against oxidative stress. As an antioxidant, glutathione “scavenges” harmful free radicals, which are byproducts of metabolism that cause damaging oxidative stress when left unaddressed. To damage cells, free radicals react with a cell’s enzymes, blocking their ability to perform their physiological function. Rather than allowing free radicals to react with cellular machinery in a damaging way, glutathione reacts with the radicals instead. Once it has reacted with as many free radicals as they can, glutathione molecules are trafficked to the bile to be degraded safely. In the liver, glutathione molecules are normally present in high concentrations. However, there are a lot of free radicals and other dangerous chemicals being generated in the liver under normal conditions and if there aren’t enough glutathione molecules in the liver to offload the free radicals being generated, damage to the liver can accumulate quickly.Using this rationale, researchers have been able to prove that mice with chronically low glutathione levels in their livers experienced a cascade of damage starting with the mitochondria of liver cells and ending with total liver failure after a month. Conversely, it is believed that higher levels of glutathione may offer greater protection from ongoing damage caused by residual toxins or free radicals. As such, some treatment providers also offer intravenous glutathione in an aqueous format for rapid replenishment of depleted reserves. Typically, however, patients take glutathione orally in a powder or pill format. When administered as a supplement, the side effects of glutathione are mild or absent, making it highly tolerable for patients.
What Is Milk Thistle?
Glutathione is a potent chemical to include in a detox regimen, but it’s even more effective when paired with milk thistle, which supports all of glutathione’s processes. Milk thistle is a common herb found worldwide, easily recognizable by its spiky purple flower and bright green stem. Significantly, the milk thistle plant contains a number of bioactive chemicals, including silybin and silymarin, which offer detoxifying benefits. While other chemicals in milk thistle may also alter liver cells, silybin and silymarin are the most studied because they are the most abundant in the plant.
Patients consume milk thistle as a liquid extract or dehydrated dietary supplement. While there’s no consensus on the quantity that patients should consume to derive benefits, researchers know that milk thistle is safe to consume at quantities far beyond those offered in supplements. The side effects of milk thistle are mild and include transient nausea, headaches, and dizziness. At high doses, milk thistle may cause diarrhea, though at lower doses the effect is merely to precipitate a bowel movement. Milk thistle appears to be safe for the liver when taken over a long period of time in patients with compromised livers.
But why is milk thistle beneficial for liver detoxing at all? In the context of the liver, milk thistle, like glutathione, behaves as an antioxidant. More importantly, milk thistle causes the liver to use glutathione more efficiently and in higher concentrations than normal.
Preventing Oxidative Stress
The antioxidant properties of milk thistle make it effective at detoxing the liver when the liver is experiencing oxidative stress. Though milk thistle scavenges free radicals, it is not a particularly outstanding scavenger when compared to glutathione. However, milk thistle possesses several unique properties which make up for its relatively weak scavenging ability. These properties tie in directly with glutathione, making the two compounds natural complements.
Uniquely among common antioxidants, milk thistle inhibits free radical formation. This effect is especially pronounced in the inhibition of free radicals generated by ethanol consumption. Ethanol consumption is one of the most egregious producers of free radicals which people regularly come into contact with, so the health-supportive effects of reducing ethanol’s oxidative impact are hard to overstate. While milk thistle won’t prevent the negative systemic effects of alcohol—like hangovers—it may help to purge the leftover aldehydes and other metabolic byproducts of ethanol which are toxic. Because milk thistle can prevent free radicals from forming, its efficacy as an antioxidant is much higher than it would seem based on its ability to scavenge free radicals alone. When used in combination with glutathione, the impact on the concentration of free radicals in the liver might be exponentially more beneficial; reducing the rate at which free radicals are formed would free up more glutathione than would otherwise be available, leading to superior trafficking of the remaining free radicals. Reducing the rate of free radical formation would also provide patients with impaired glutathione synthesis or systemically high oxidative stress—as is commonly experienced in people with a variety of health conditions, including autism spectrum disorder—more time between experiencing oxidative stress and damage to their tissues.
Furthermore, milk thistle could ostensibly be used to preventively recruit extra glutathione to the liver in situations where the patient expects to be placing a lot of oxidative stress on their system. While milk thistle hasn’t been explored in this context in humans, rats which received a mixture of chemicals derived from milk thistle experienced 40% fewer instances of enzyme degradation when later exposed to a chemical cocktail designed to induce high levels of oxidative stress compared to controls. Though this activity is not “detoxification” per se, preventing damage from accumulating in the first place serves the same purpose.
Chemicals derived from milk thistle also improve the efficacy of glutathione by preventing its breakdown by liver enzymes in addition to recruiting glutathione molecules to the site of oxidative stress. This leads to a higher concentration of glutathione than would otherwise be present, providing a superior level of protection. To accomplish this feat, milk thistle inhibits certain enzymes which degrade glutathione like glutathione reductase and glutathione peroxidase. While these enzymes are necessary for glutathione to offload its free radical cargo outside the liver, their presence inside the liver is detrimental for the purpose of detoxing. When these enzymes can’t impact glutathione, glutathione remains in the high oxidative stress area for longer, reducing damage. This effect makes milk thistle an excellent complement to glutathione for patients who expect to confront oxidative stress in the near future.
Supporting Liver Cell Function
In addition to recruiting antioxidants and supporting their function, milk thistle also improves mitochondrial function. As the “powerhouse” of the cell, the mitochondria is an organelle which transforms chemicals into a format that cells can use for energy. This process would normally increase the rate of free radical generation, but this effect is mitigated owing to milk thistle’s attraction of glutathione.
When liver cells have a higher supply of chemical energy than usual, they can perform more cycles of toxin removal than usual. As such, liver cells with overpowered mitochondria operate more effectively so long as there is enough milk thistle present. The end effect is that blood exiting the liver has fewer toxins than it would otherwise. Likewise, a higher energy supply allows liver cells to traffic glutathione to problem areas more expediently. Later, cells with more energy can quickly remove and recycle the saturated glutathione molecules, closing the loop much more rapidly. For healthy people, the difference is likely negligible, but for those with lowered liver function, high levels of oxidative stress, or a heavy toxin load, the impact could be significant.
Even for those who are healthy, improving the amount of chemical energy generated by the mitochondria has other beneficial effects for liver cells. Research shows that, when exposed to a high concentration of toxic chemicals which would typically kill liver cells, cells which received a dosage of milk thistle experienced lower mortality than those which did not. This phenomenon can be attributed to the increased glutathione concentrations caused by the administration of milk thistle.
These effects carry over into living patients with dramatic results. In a human trial investigating the impact of milk thistle extract on people with liver damage caused by hepatitis B or C, patients who received milk thistle extract experienced a 50% lower risk of mortality caused by liver pathologies. Though this was only the case in patients also receiving standard pharmaceutical treatments to support liver function—milk thistle alone did not reduce mortality—the picture is clear: patients with weakened livers have better chances with milk thistle than without. This is due to the fact that cells with extra chemical energy are more resilient when faced with extreme conditions because they can export toxins using glutathione more efficiently. They’re also more resilient when toxins are degraded before they can cause permanent damage.
Supporting the Detoxification Process
In terms of direct detoxification of the liver, both glutathione and milk thistle are effective at degrading some of the most dangerous toxins that may be present in the liver. For example, milk thistle lowers the cellular concentration of a toxic chemical called malondialdehyde by causing it to degrade into harmless components. Many other aldehyde class chemicals are created by metabolic breakdown of ethanol and are similarly degraded by milk thistle before they can do any damage. Unlike the aldehydes generated by metabolism of ethanol, malonaldehyde is itself a product of reactive oxygen species reacting with other physiological molecules like phospholipids, which means that its synthesis has already caused damage to occur. While most patients may not know about malonaldehyde, it’s doubtlessly something their livers have encountered; whenever a reactive oxygen species gains access to a polyunsaturated lipid molecule, the ensuing chemical reaction will generate a molecule of malonaldehyde.Like its precursors, malonaldehyde is highly reactive, but it reacts with a different set of targets than its precursors; rather than reacting with enzymes, malonaldehyde reacts with DNA. After this reaction, the section of DNA with which the malonaldehyde is no longer “readable” by cellular machinery. In isolation, rendering a section of DNA unreadable would mean that the cell could not implement whichever instructions were coded in that region—problematic, but not catastrophic, as there are many redundant copies of DNA within the cell. The damage to the DNA is not so manageable when caused by malonaldehyde, however. This is because malonaldehyde persists for long after the initial reaction period as a mutagen embedded with the DNA. These embedded mutagens are called DNA adducts, and they’re highly correlated with developing cancers in whichever cell type they’re found. The fact that milk thistle appears to degrade malonaldehyde, therefore, means that it might prevent damage to DNA that would lead to cancer. While milk thistle’s cancer-preventing effects have been subject to a handful of clinical trials, the results on its efficacy remain inconclusive. Nonetheless, milk thistle’s beneficial impact on liver cells is proven, as is its extensive antioxidant capability.
Glutathione, on the other hand, is adept at helping the liver to purge some of its most dangerous contaminants which don’t bind to DNA. For example, in one study, researchers found that when glutathione was depleted from liver cells, they died much faster when exposed to cadmium. Cadmium is a metal found in a variety of products, including certain paints, toys, alloys, and plastics as well as tobacco smoke, batteries, solar panels, and older steel. This material is toxic to cells and difficult to remove from the liver without expensive and time-consuming metal chelation therapy. Even though the dangers of cadmium are well-known, many products still contain cadmium because it is not acutely toxic in commercial concentrations. But despite a lack of acute toxicity, chronic exposure can cause cellular dysfunction in the liver, which can have a detrimental impact on health. Glutathione can protect against such dysfunction; the study demonstrated that when glutathione was boosted to greater than normal levels, liver cells were able to recover from cadmium exposure and maintain normal functioning. This effect of glutathione has been documented with other metals ranging from iron to lead.
Given that metal chelation therapy is typically the only other option which patients might have to address the toxicity caused by these metals, glutathione supplementation as part of a detox regimen could make a meaningful difference. Especially for patients who have chronic conditions which cause oxidative stress from other sources, reducing the stress caused by metal toxicity may provide significant benefits
The Future Of Natural Liver Detox
Ongoing research is attempting to shed more light on the scope and depth of the combination of milk thistle and glutathione and its potential for purging the liver and the next few years will likely be replete with new findings. However, patients seeking a more effective detoxification therapy for their livers can already benefit from therapeutic glutathione and milk thistle use, particularly as sophisticated new supplements enter the market. These supplements may be used both as a routine preventive measure and preemptively when patients expect to be drinking alcohol or exposing themselves to other sources of oxidative stress like tobacco smoke. For patients who already have weakened livers and seek to boost their liver’s ability to process toxins in the face of greater-than-usual oxidative stress, a milk thistle and glutathione detox regimen could also be a valuable addition to conventional therapies. Taken together, these supplements offer patients with a natural, highly tolerable, and potent combination to protect health and well-being, potentially enhancing both longevity and quality of life.
Works Cited
Chen Y, Yang Y, Miller ML, Shen D, Shertzer HG, et al. 2007. Hepatocyte-specific Gclc deletion leads to rapid onset of steatosis with mitochondrial injury and liver failure. Hepatology. 45:1118–1128. https://www.ncbi.nlm.nih.gov/pubmed/17464988
Comoglio A, Leonarduzzi G, Carini R, Busolin D, Basaga H, et al. 1990. Studies on the antioxidant and free radical scavenging properties of Idb 1016 a new flavanolignan complex. Free Radical Research Communications. 11:109–115. https://www.ncbi.nlm.nih.gov/pubmed/2074043
Comoglio A, Tomasi A, Malandrino S, Poli G, Albano E. 1995. Scavenging effect of silipide, a new silybin-phospholipid complex, on ethanol-derived free radicals. Biochemical Pharmacology. 50:1313–1316. https://www.ncbi.nlm.nih.gov/pubmed/7488251
Deleve L, Kaplowitz N. 1990. Importance and regulation of hepatic glutathione. Seminars in Liver Disease. 10:251–266. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2596047/?page=2
Pietrangelo A, Montosi G, Garuti C, Contri M, Giovannini F, et al. 2002. Iron-induced oxidant stress in nonparenchymal liver cells: mitochondrial derangement and fibrosis in acutely iron-dosed gerbils and its prevention by silybin. Journal of Bioenergetics and Biomembranes. 34:67–79. https://www.ncbi.nlm.nih.gov/pubmed/11860182
Pompella A, Visvikis A, Paolicchi A, Tata VD, Casini AF. 2003. The changing faces of glutathione, a cellular protagonist. Biochemical Pharmacology. 66:1499–1503. https://www.ncbi.nlm.nih.gov/pubmed/14555227
Rambaldi A, Jacobs BP, Gluud C. 2007. Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases. Cochrane Database of Systematic Reviews. https://www.ncbi.nlm.nih.gov/pubmed/17943794
Zhang J, Zhou X, Wu W, Wang J, Xie H, Wu Z, et al. 2017. Regeneration of glutathione by alpha-lipoic acid via Nrf2/ARE signaling pathway alleviates cadmium-induced HepG2 cell toxicity. Environmental Toxicology and Pharmacology. 51:30–37. https://www.ncbi.nlm.nih.gov/pubmed/28262510