Beyond Detox: Maximizing Liver Health Through Natural Substances and Research Insights
The liver is perhaps one of the most vital organs in the body. This organ is involved in numerous crucial biological roles, acting as a check-and-balance for more than one mechanism. It is reasonable to say that most people are familiar with the liver’s role in removing toxins from the blood, such as alcohol and drugs, but the liver does so much more than act as a filter. This article will review the roles that the liver plays, common diseases of the liver, and natural, research-supported substances to help maximize liver health.
What Does the Liver Do?
First and foremost, the liver processes blood and toxins. The liver acts as a sponge that breaks down, balances, and creates nutrients and metabolizes drugs into forms that are easier for the rest of the body to use or that are non-toxic. Perhaps the most notable is how the liver breaks down acetaminophen, aka Tylenol [1].
A lot of times, when a person overdoses on medication, it is because that person’s liver is overwhelmed in attempting to metabolize the drug.
The liver also processes bile. Bile is a sticky, yellow-green digestive fluid made by the liver and comprises bile acids, cholesterol, water, phospholipids, electrolytes, and metals [2]. Bile also contains waste products from the liver, such as bilirubin and hemoglobin. Bile is stored in the gallbladder and helps to carry away waste and break down fats in the small intestine during digestion so that they can be more easily absorbed.
The liver also significantly regulates blood sugar by balancing glucose uptake, storage, and release via glycogenesis, glycogenolysis, and gluconeogenesis.
- Glycogenesis: When blood sugar levels are high, the liver stores glucose as glycogen, a complex carbohydrate. This process is stimulated by insulin, a hormone produced by the pancreas. When insulin binds to liver cells, it triggers the conversion of glucose into glycogen, which is then stored in the liver [3] [4] [5].
- Glycogenolysis: When blood sugar levels are low, the liver releases glucose from stored glycogen through glycogenolysis. This is triggered by the hormone glucagon, which is released by the pancreas in response to low blood sugar levels. Glucagon stimulates the breakdown of glycogen into glucose, which is then released into the bloodstream [3] [4] [5].
- Gluconeogenesis: The liver also produces glucose through gluconeogenesis, which occurs when the body needs more glucose than it is making. This process involves the conversion of non-carbohydrate sources, such as amino acids and lactate, into glucose [3] [4] [5].
This complex process helps maintain normal blood sugar levels and ensures the body has a steady supply of glucose for energy production and other bodily functions.
The liver also plays a crucial role in regulating blood clotting. The liver produces most of the proteins found in blood, including albumin, which helps to regulate blood volume and distribution of fluids in the body by keeping fluids in the bloodstream from leaking into surrounding tissue [6].
The liver also produces coagulation factors, essential for blood clotting and activated when bleeding occurs. These factors help to form a clot and prevent a hemorrhage [7]. The bile that the liver produces also helps to absorb and synthesize vitamin K, and if vitamin K levels are too low, a person is likely to experience uncontrollable bleeding [7] [8] [9].
Further, the liver regulates blood clotting by breaking down old or damaged blood cells, which helps to maintain healthy blood circulation. The liver’s ability to regulate blood clotting and break down cells is essential for maintaining overall blood health and preventing conditions such as hemophilia, a bleeding disorder characterized by a deficiency of coagulation factors [10].
The liver also plays a crucial role in producing proteins and hormones secreted into the blood. These can intuitively be grouped into categories:
- Major Plasma Proteins: All plasma proteins except globulins are synthesized in the liver [11]. Plasma proteins are a vital component of blood plasma, accounting for about 7.4% of its composition. We’ve already discussed the major plasma protein albumin, which regulates the amount of fluid in the blood vessels and assists in the transport of lipids and steroid hormones. Fibrinogen is also essential for blood clotting and converts to insoluble fibrin when blood vessels are damaged.
- Carrier Proteins: The liver also creates carrier proteins, which carry hormones and other substances through the bloodstream to transport them throughout the body. Albumin, again, is also a carrier protein, as it carries thyroid hormones and other hormones, particularly fat-soluble ones, fatty acids to the liver, various drugs, and calcium throughout the body. Other notable carrier proteins include ceruloplasmin (carries copper), transcortin (carries cortisol, aldosterone, and progesterone), retinol-binding proteins (carries retinol, aka vitamin A), sex hormone-binding globulin (carries sex hormones, specifically testosterone and estradiol), thyroxine-binding globulin (carries the thyroid hormones T3 and T4), transthyretin (carries T4), transferrin (carries iron), and vitamin D-binding protein (carries vitamin D).
- Hormones: The liver also creates hormones. It creates FGF21, a protein hormone that induces mitochondrial oxidation of fatty acids, hepatic gluconeogenesis (which we discussed earlier under “regulating blood sugar”), and ketogenesis in response to fasting. The liver also creates hepcidin (a peptide hormone that regulates iron balance), insulin-like growth factor 1 (a hormone that plays a vital role in childhood growth), and thrombopoietin (a hormone that regulates the production of platelets by the bone marrow).
There are many more proteins and hormones that the liver produces and secretes and, if in excess, removes. However, this article aims to provide an overview, so we covered a wide range of proteins and hormones to illustrate the extraordinary degree to which the liver impacts nearly every aspect of the body.
Common Diseases of the Liver
Due to its multifaceted roles within the body’s mechanisms, the liver is susceptible to myriad diseases, each manifesting in unique symptoms. For instance, individuals may exhibit jaundice, characterized by yellowish skin and eyes, or present with pale, bloody, or black stools, an enlarged abdomen, or encephalopathy, which perturbs mood, sleep, and cognition [12].
Among the most recognized liver diseases is hepatitis, an inflammation of the liver encompassing five distinct types: A through E.
- Hepatitis A, a viral form, spreads through contaminated food or water. Symptoms may resolve spontaneously, albeit recovery may extend over several weeks.
- Hepatitis B, another viral variant, can be either acute or chronic, often transmitted through sexual contact, with no definitive cure.
- Hepatitis C, also viral, can manifest acutely or chronically and typically spreads through blood contact.
- Hepatitis D, a severe type of hepatitis, only arises in individuals already infected with hepatitis B.
- Hepatitis E, primarily caused by contaminated water, resolves within weeks without specific treatment.
Fatty liver disease represents another prevalent category comprising alcoholic and non-alcoholic subtypes.
Alcoholic fatty liver disease, as the name suggests, stems from excessive alcohol consumption. Conversely, non-alcoholic fatty liver disease, a more intricate condition, entails the accumulation of fat in the livers of individuals with minimal alcohol intake. Its prevalence in the United States has surged from 15% in 2005 to 25% by 2010, often coinciding with metabolic comorbidities such as obesity, type-2 diabetes, dyslipidemia, and metabolic syndrome [13].
Overall, fatty liver disease predominantly results from years of lifestyle choices, whether involving heavy alcohol consumption or not. Lifestyle modifications, including exercise and dietary adjustments, may offer management strategies. However, failure to address these issues may culminate in liver cirrhosis or failure.
Autoimmune liver conditions often arise, which is where the body’s immune system mistakenly attacks healthy liver cells. For example, autoimmune hepatitis is where the body’s attacking of healthy liver cells causes liver inflammation.
Additionally, both primary biliary cirrhosis and primary sclerosing cholangitis represent additional autoimmune disorders, causing damage to the bile ducts within the liver, potentially resulting in cirrhosis or liver failure.
Drug-induced liver disease is another type of common liver disease, characterized by liver damage due to excessive exposure to certain medications or supplements. While acetaminophen is commonly associated with drug-induced liver disease, any substance taken in excess poses a similar threat [14].
Statin drugs, a class of medications used to lower cholesterol levels in the blood, work by inhibiting the production of cholesterol in the liver. These drugs are infamously renowned for liver damage [15] [16] [17] [18] [19] [20] [21].
Liver cancer is another type of liver illness. Liver cancer generally starts as either a single large lesion or many small lesions on the liver. Secondary liver cancer denotes instances where cancer originates elsewhere in the body before metastasizing to the liver.
Cirrhosis of the liver is marked by liver scarring resulting from various liver ailments and poses a significant health concern because it effectively prevents the damaged part of the liver from functioning properly. Although the liver possesses some regenerative abilities, such processes often result in scar tissue accumulating over time.
Natural Compounds for Liver Health
Several substances have been studied for their benefits regarding liver health. Generally, researchers conduct these studies by chemically inducing liver damage in animals and providing the animal with the substance.
Curcumin, or turmeric, has been well studied.
In a 2017 study, researchers examined the effects of curcumin, a compound found in turmeric, against the impact that acute and chronic stress had on the body. Specifically, the researchers were interested in how curcumin dealt with harmful ROS molecules [22].
The researchers found that when the body is under short-term stress, its natural defense system against these harmful molecules works fine, but the production of certain liver enzymes increases. However, with long-term stress, the liver enzymes increase even more, and the body’s defense system becomes weaker [22].
They also discovered that in long-term stress, a specific type of harmful molecule produced in the cell’s energy-making structures (ER) builds up, causing more damage. This stress also messes up how proteins fold inside the ER, leading to further problems in the liver [22].
However, when they treated the stressed bodies with curcumin or a curcumin-rich extract from turmeric, they noticed that curcumin helped the liver recover from the damage caused by stress, regardless of whether it was short-term or long-term [22].
So, in simpler terms, curcumin seems to help protect the liver from the harmful effects of stress, whether short-term or long-term. This suggests that curcumin or turmeric extract could help maintain liver health, especially during stressful times [22].
Moreover, in a 2011 animal study, scientists again delved into the potential protective powers of curcumin. As we’ve reviewed, the liver is a crucial organ that can take a hit from toxic substances like carbon tetrachloride (CCl4), but research suggests that curcumin might come to the rescue. The researchers noted some outcomes by giving rats curcumin supplements [23].
First, curcumin increased the protein levels called APE1/Ref-1 in the rats’ livers. This protein acts as a cellular superhero, repairing DNA and dialing down inflammation, essential for keeping liver cells healthy [23].
Second, curcumin also appeared to shield the liver from oxidative stress. By bolstering the liver’s natural defenses and lowering levels of damaging fats, curcumin showed promise in keeping liver tissue looking and functioning at its best. Moreover, curcumin seemed to tame inflammation by reducing levels of inflammatory substances, potentially preventing the internal chaos that leads to liver damage [23].
Third, the researchers noted that curcumin did more than prevent harm—it seemed to turbocharge the liver’s protective mechanisms even more in stressed-out rats [23]. This falls in line with what the researchers observed in the 2017 study.
Many, many studies investigate the benefits of curcumin on liver health [24] [25] [26] [27].
And curcumin is not the only natural substance studied for its benefits on liver health. Selenium has also been researched.
In a 2019 study, researchers acknowledged that certain pain medications can lead to liver injury [27]. The inflammation triggered by certain substances, known as inflammagens, is thought to play a role in this drug-induced liver injury.
In light of this, researchers wanted to see if curcumin and selenium, both known for their anti-inflammatory properties, could offer protection against liver damage caused by a combination of lipopolysaccharide (LPS) (a bacterial toxin) and diclofenac (a pain medication) [27].
In the study, rats were given curcumin and/or selenium for a week before being exposed to a combination of LPS and diclofenac. The results showed that the rats exposed to this combination experienced liver damage, as evidenced by elevated liver function markers in their blood and changes in liver tissue when examined under a microscope. Additionally, there were signs of increased oxidative stress, where harmful molecules were causing damage, and decreased antioxidant defenses in the liver [27].
However, the rats that received curcumin and/or selenium showed protection against liver injury. Not only did their liver tissues look healthier, but they also had lower levels of oxidative stress and higher levels of antioxidants. Furthermore, inflammatory markers in their blood and liver were reduced, indicating less inflammation. The researchers suggested that curcumin and selenium could help prevent and reduce the severity of liver injury during acute inflammation, potentially offering a natural way to support liver health, especially for those taking diclofenac or similar medications [27].
Alpha-lipoic acid (ALA) is another substance that has been researched for its liver protective effects.
In a handful of studies, ALA was identified to have shown a protective effect on various chemically-induced liver injuries [28] [29] [30].
Chronic exposure to chlorpyrifos (CPF) pesticides can lead to liver damage, but ALA might offer protection [28]. In a 2018 study, rats were given ALA alongside CPF to see if it could protect against liver harm. The researchers observed that ALA improved liver function and lessened tissue damage caused by CPF. Additionally, ALA helps reduce oxidative stress in the liver by lowering harmful molecules while increasing the activity of antioxidant enzymes. Further, ALA seemed to have anti-apoptotic effects, which helped prevent cell death in the liver [28].
Fluoride in water and food can harm the liver, but ALA may also offer protection. ALA was given alongside fluoride in a 2022 study with mice to see if it could protect the liver. The results showed that, again, ALA lessened liver damage caused by fluoride by reducing oxidative stress and lipid peroxidation. Moreover, ALA seemed to prevent a specific type of cell death called ferroptosis by regulating certain pathways related to iron metabolism and lipid peroxidation. Interestingly, ALA didn’t seem to affect mitochondrial free radicals. This suggests that ALA could be a potential treatment for preventing fluoride-induced liver injury by inhibiting ferroptosis [29].
Finally, sodium valproate, another medication, can harm the liver, but once again, in a 2020 study, researchers looked at the possible protective benefits of ALA. In this study with mice, ALA was given alongside sodium valproate to see if it could protect the liver from damage. Researchers found that ALA improved the appearance of liver tissue and reduced signs of damage caused by sodium valproate. Even after two weeks of sodium valproate treatment, ALA restored the liver’s structure to a point closer to normal. The researchers concluded that ALA could be beneficial in reducing liver injury caused by sodium valproate [30].
And it doesn’t have to be a chemical, either. Substances in everyday foods, such as high fructose corn syrup (HFCS), can cause liver problems.
In a 2020 study, researchers investigated how chronic consumption of HFCS affects the liver and whether ALA could offer protection against damage. They conducted their experiment using 24 rats, dividing them into three groups: one group drank HFCS-laced water for ten weeks, another group drank the same HFCS water but also received ALA for the last six weeks, and the third group served as a control and didn’t receive any treatment [31].
At the end of the ten weeks, the rats were examined. The rats in the HFCS group showed higher liver enzyme levels called aspartate aminotransferase (AST) in their blood, indicating liver damage. Additionally, there was an increase in oxidative stress, as evidenced by higher levels of malondialdehyde (MDA) in their liver tissues, along with a decrease in the activity of an important antioxidant enzyme called catalase (CAT). Moreover, there was an increase in the expression of caspase-3, a marker for cell death, suggesting increased apoptosis (cell death) in the liver [31].
However, the rats that received ALA alongside HFCS showed promising results. The MDA, CAT, and caspase-3 levels were brought back to near-normal levels, indicating that ALA administration helped counteract the harmful effects of HFCS on the liver. This suggests that HFCS consumption can indeed lead to liver damage through oxidative stress and apoptosis, but ALA treatment can help mitigate these effects, offering a potential therapeutic approach to protect against HFCS-induced liver toxicity [31].
This also may help to explain why lifestyle and diet, i.e., chronic, increased consumption of HFCS-rich foods, contributes to fatty liver disease.
Further, ALA has also been shown to protect against liver damage caused by cigarette smoke.
In a 2021 study, researchers looked at how ALA could help combat the harmful effects of cigarette smoke on the liver. They conducted their experiment using female rats, dividing them into three groups. One group was exposed to fresh air, another to cigarette smoke twice daily, and the third to cigarette smoke along with daily ALA supplements for eight weeks.
The results were this: rats exposed to cigarette smoke showed increased levels of markers for liver damage, such as MDA and AST, along with decreased antioxidant activity. However, the group that received ALA alongside cigarette smoke showed improvements in liver function and reduced markers of damage, indicating that ALA might help protect the liver from the harmful effects of smoking [32].
Milk thistle extract is generally very beneficial for liver health because of its active ingredient, silymarin.
In a 2019 study, researchers conducted a meta-analysis of randomized controlled trials investigating the protective effects of silymarin on drug-induced liver injury from antituberculosis medications [33]. Their analysis included data from five RCTs involving 1198 patients, split between those who took silymarin and those who didn’t [33].
Overall, they found that silymarin significantly reduced the risk of developing liver damage caused by antituberculosis drugs by week 4 [33].
Furthermore, silymarin seemed to have a protective effect on liver function, improving markers like ALT, AST, and ALP levels in patients taking anti-TB drugs. Interestingly, silymarin didn’t cause more adverse effects than the placebo [33].
A collection of studies have found silymarin to be beneficial for non-alcoholic fatty liver disease [34] [35] [36] [37] [38], hepatitis C [39] [40], and liver cancer [41] [42] [43].
Finally, N-acetyl cysteine (NAC) is another substance renowned for its researched-supported, liver-protective effects.
A 2010 study researching the protective benefits of both curcumin and NAC found that both substances could protect the liver from chemically-induced liver damage [26].
ALA also plays a protective role in the event of an acetaminophen overdose.
For example, when a person takes acetaminophen, the liver metabolizes – or processes – acetaminophen by binding acetaminophen to a sulfate and glucuronide molecule so that the liver can eliminate acetaminophen from the body. However, when a person takes too much acetaminophen to a degree that overwhelms the sulphation and glucuronidation pathways, the liver then turns to another option: the P-450 system.
The P-450 is a family of enzymes that process various proteins and chemicals; generally, these enzymes don’t cause an issue. However, when P-450 is called to process acetaminophen, these enzymes create a metabolite called NAPQI. This metabolite is highly toxic and would generally be neutralized by the glucuronidation pathway. But, when a person takes too much acetaminophen, the glucuronidation pathway is already overwhelmed, so NAPQI builds up, the liver’s stores of glutathione – which widely supports liver detoxification – become depleted, and the free NAPQI attacks structures on cell membranes, causing significant liver damage [44].
In a 2018 publication investigating acetaminophen and acute liver failure, researchers investigated ALA, its protective effects, and how it may help prevent acute liver failure in patients who ingest too much acetaminophen [44].
Remarkably, the researchers noted that “NAC, a GSH precursor, is an established antidote for APAP overdose and should be given in all patients with APAP hepatoxicity, as well as in patients at significant risk for developing hepatotoxicity” [44].
This is likely because NAC is a precursor to glutathione, meaning that NAC supplementation helps the body replace glutathione, dubbed the body’s master antioxidant. Glutathione is directly relied upon in an acetaminophen overdose because of the overutilization, as mentioned earlier, regarding the sulphation and glucuronidation pathways. So, in the event of an acetaminophen overdose, emergency rooms often provide the body with large doses of NAC to facilitate glutathione detoxification [45].
Healthmasters’ Liver Support
Healthmasters’ Liver Support contains four critical ingredients for liver health: selenium, milk thistle extract, ALA, and NAC. To read more about these ingredients, check out Liver Support: A Review of Ingredients.
If you have any questions about Healthmasters' Liver Support, please call our office at 800.726.1834.
References:
[1] https://www.medicinenet.com/tylenol_liver_damage/article.htm
[2] https://www.verywellhealth.com/definition-of-bile-1759867
[3] https://pubmed.ncbi.nlm.nih.gov/10448530/
[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892876/
[5] https://pubmed.ncbi.nlm.nih.gov/9333317/
[6] https://columbiasurgery.org/liver/liver-and-its-functions
[7]https://mountainspringsrecovery.com/health/what-does-the-liver-do-and-why-is-it-so-important/
[8] https://badgut.org/information-centre/a-z-digestive-topics/the-liver-an-amazing-organ/
[9] https://www.ncbi.nlm.nih.gov/books/NBK279393/
[10] https://www.cdc.gov/ncbddd/hemophilia/facts.html
[11] https://pubmed.ncbi.nlm.nih.gov/13130789/
[12] https://www.hep.org.au/liver-health/signs-and-symptoms-of-liver-damage-or-disease/
[13] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5743497/
[14] https://www.ncbi.nlm.nih.gov/books/NBK548733/
[15] http://www.ncbi.nlm.nih.gov/pubmed/17662392
[16] http://www.ncbi.nlm.nih.gov/pubmed/12867804
[17] http://www.ncbi.nlm.nih.gov/pubmed/1520752
[18] http://www.ncbi.nlm.nih.gov/pubmed/20488911
[19] http://www.ncbi.nlm.nih.gov/pubmed/16393626
[20] http://www.ncbi.nlm.nih.gov/pubmed/19198578
[21] http://www.ncbi.nlm.nih.gov/pubmed/19332511
[22] https://pubmed.ncbi.nlm.nih.gov/28747775/
[23] https://pubmed.ncbi.nlm.nih.gov/21911894/
[24] https://www.ncbi.nlm.nih.gov/pubmed/31694300
[25] http://www.ncbi.nlm.nih.gov/pubmed/16956363
[26] http://www.ncbi.nlm.nih.gov/pubmed/21175036
[27] https://www.ncbi.nlm.nih.gov/pubmed/31654258
[28] http://www.ncbi.nlm.nih.gov/pubmed/29500983
[29] http://www.ncbi.nlm.nih.gov/pubmed/36459405
[30] https://www.ncbi.nlm.nih.gov/pubmed/32636594
[31] https://pubmed.ncbi.nlm.nih.gov/32636594/
[32] https://pubmed.ncbi.nlm.nih.gov/34084105/
[33] https://pubmed.ncbi.nlm.nih.gov/30733935/
[34] https://www.ncbi.nlm.nih.gov/pubmed/29245314
[35] https://www.ncbi.nlm.nih.gov/pubmed/23087748
[36] https://www.ncbi.nlm.nih.gov/pubmed/28419855
[37] https://www.ncbi.nlm.nih.gov/pubmed/27158393
[38] https://www.ncbi.nlm.nih.gov/pubmed/28454924
[39] https://www.ncbi.nlm.nih.gov/pubmed/27842532
[40] https://www.ncbi.nlm.nih.gov/pubmed/29135373
[41] https://www.ncbi.nlm.nih.gov/pubmed/16675592
[42] https://www.ncbi.nlm.nih.gov/pubmed/26189518
[43] https://www.ncbi.nlm.nih.gov/pubmed/26011349
[44] https://www.sciencedirect.com/science/article/abs/pii/S1089326118300072?via%3Dihub
*These statements have not been evaluated by the Food and Drug Administration. Healthmasters' Liver Support is not intended to diagnose, treat, cure, or prevent any disease.
