The liver is a highly metabolic organ with a range of functions which are essential for digestive health, hormone regulation as well as the detoxification and excretion of waste products. If the liver is under stress, it can contribute to multiple symptoms associated with excess toxicity, hormone dysregulation and digestive dysfunction. Hence, poor liver health is a major contributor to chronic disease and is associated with a decline in wellbeing.
The liver is also an essential regulator of blood glucose, cholesterol and clotting factors therefore, liver health has a significant influence on cardiovascular function. It is also intrinsically linked to the digestive system; waste products are excreted from the liver to the digestive system via the bile and absorption of products from the digestive system are transported to the liver for filtration. This filtration process protects multiple bodily systems, including the immune system by modifying the content of infectious agents in the bloodstream.
It is important to consider that the liver must be resilient to oxidative damage, stress and inflammation, to protect and support its optimal function. In this week’s blog we will look at the detoxification processes of the liver, dysfunction which contributes to poor liver health and associated conditions, and at how to support liver function.
The liver is responsible for the detoxification and excretion of toxicants, which includes a wide variety of both intrinsic and extrinsic substances such as alcohol, medications, heavy metals, environmental toxicants, waste hormones and byproducts.
These products tend to be fat soluble and therefore cannot be easily excreted in their current form. They need to go through two processes of detoxification before they can be excreted into the digestive system and out of the body.
Firstly, toxicants must be made water soluble and secondly, they need to be bound to another molecule to make then safe or inactive to allow effective removal from the body. The two processes are known as phase 1 and phase 2.1
Phase 1 is responsible for making toxicants water soluble. It involves a group of enzymes known as cytochrome P450 enzymes; there are several hundred of these which have affinities for different substances. These will catalyse reactions which make lipid soluble toxins water soluble either by oxidation, reduction, hydrolysis, hydration or dehalogenation.
These reactions are supported by the availability of nutrients including B2, B3, B6, folate, B12, glutathione, branched chain amino acids, flavonoids and phospholipids.1
Unfortunately, the process of making these toxicants water soluble means that they become more damaging as they have the potential to be more mobile, as opposed to being contained in adipose (fat) tissues, thereby creating more damage. These are referred to as reactive oxygen intermediates, and they need to be further detoxified as soon as possible.
In addition, the oxidant superoxide is produced during phase 1 reactions. Both superoxide and reactive oxygen intermediates are unstable molecules and create oxidative stress, damage and eventually inflammation. Excess amounts of these molecules can contribute to liver damage and dysfunction.
Therefore, the presence of antioxidants to protect the liver from damage as well as support for the activity of the second phase (phase 2) are essential for liver health.1
Phase 2 is involved in conjugation pathways; this means that the now water-soluble substance is bound to another molecule to make it inert so it can be safety excreted via the bile and the digestive system. Each substance will be conjugated via one of six pathways:1
- Sulfation – addition of a sulphur molecule – supported by sulphur containing amino acids (methionine and cysteine) and sulphurous and cruciferous vegetables (e.g. garlic, onion, broccoli, cauliflower andkale)
- Glucuronidation – addition of glucuronic acid – supported by cruciferous vegetables
- Glutathione conjugation – – glutathione is our major intracellular antioxidant which you can take orally and is also supported by glycine, N-acetyl cysteine, vitamin C and selenium
- Acetylation – attaches acetyl A to toxin, supported by B5, vitamin C and short chain fatty acids such as butyric acid produced by gut flora
- Methylation – attaches a methyl group to toxin. Any methyl donor such as methylcobalamin (B12) or methylfolate as well as methylation supporting nutrients (B6 and zinc) are important for this
- Amino acid conjugation – attaches to an amino acid – therefore adequate protein intake is essential for normal liver function
Imbalanced phase 1 and 21,2
In some individuals there can be a disparity between phase 1 activation and phase 2. Often phase 1 can be like traveling along the motorway but when we get off at the junction towards phase 2 there is a bottle neck leading to a traffic jam.
At this point we have high amounts of reactive oxygen intermediates, which as mentioned are highly oxidative (damaging). These can build up and create an excessive amount of oxidative stress, leading to mitochondrial and cellular damage creating dysfunction and inflammation.
Therefore, if the liver is under stress, it is important to support antioxidant pathways and also to provide nutrients which both support and upregulate phase 2 to help reduce the backlog.
Antioxidants and liver health
Antioxidants donate electrons to unstable molecules and thereby reduce free radicals and reactive oxygen species. They play an essential role in helping to protect the liver against reactive metabolites. The endogenous, intracellular antioxidant glutathione plays an important role in liver protection and also supports phase 2 glutathione conjugation. Nutrients including N-acetyl cysteine, vitamin C and selenium support glutathione production.3,4
Polyphenols – are phytonutrients which have antioxidant capabilities and therefore can support the neutralisation of reactive intermediates. Flavonoids and carotenoids have also been shown to upregulated phase 2 detoxification pathways. Hence, they should be considered an important intervention to support liver health.5,6
The gut and the liver work very closely together as the majority of waste products are excreted via the bile and into the gut. In addition, the microbiome itself also plays a role in the production of waste products and supporting detoxification and excretion.
The intestinal microbiota produces ethanol, ammonia, and acetaldehyde; these products may influence liver function as they need to be detoxified. Alterations in the intestinal microbiota can induce and promote liver damage e.g., through mechanisms such as activation of Kupffer cells (immune cells in the liver) by bacterial endotoxins. Also, the bowel is an important elimination route for toxins bio-transformed by the gut itself and liver (and excreted in bile).
Hence the health of the gut and liver are intrinsically linked, and it is important to support both and be aware of the impact of gut health.7
Liver health and hormone balance – oestrogen dominance
Liver dysfunction can be associated with a reduced ability to detoxify and excrete waste hormones, leading to hormone imbalances, in particular oestrogen dominance. Oestrogen dominance is associated with many reproductive dysfunctions including infertility, endometriosis, premenstrual syndrome and polycystic ovary syndrome and has been shown to be a mediator of oestrogen- related cancers. Therefore, in any oestrogen dominant condition, as mentioned above, liver support should be considered.1
In the case of oestrogen dominance, it is also worth noting the importance of the gut-liver axis. Waste products are removed from the liver into the digestive system via bile. When the waste products enter the gut, they should then be excreted from the body. However, if there is an imbalance of the microbiome, known as dysbiosis, the gut flora can produce an enzyme known as beta-glucuronidase.
This enzyme can cleave oestrogen that has been conjugated in phase 2 by glucuronidation from its carrier molecule (glucuronic acid). In doing so, this allows oestrogen to be free and can then be actively reabsorbed and recirculate in the body. This gives the liver extra workload and also increases oestrogen levels, leading to oestrogen dominance.8,9
Oxidative stress and mitochondrial dysfunction are associated with hepatocyte injury (damage to liver cells). This is also part of the pathophysiology of non-alcoholic fatty liver disease (NAFLD), where the liver accumulates fat. Obesity and insulin resistance play a role in the increased production of free fatty acids from glucose within the liver.
When this is combined with tissue damage and mitochondrial dysfunction, the free fatty acids cannot be effectively taken up by peripheral adipocytes and fat can accumulate in the liver. This situation drives further liver injury, mitochondrial dysfunction and therefore fatty acid accumulation, leading to NAFLD and can eventually lead to liver cirrhosis, widespread fibrosis of the liver which dramatically reduces liver function.1,10
Other symptoms associated with liver dysfunction include:
- Weight gain
- Headaches and migraine
- Digestive symptoms
- Poor immunity
- Food and chemical sensitivities
- Skin complaints
- Hormonal imbalance
Natural ways to look after your liver health
Your liver needs optimal levels of amino acids, antioxidants, vitamins and minerals (identified above) in order to function properly – and we also need to consider the pressure we put on the liver to detoxify, from poor diet as well as environmental stressors.
You can minimise your exposure to toxins and reduce the burden on your liver by:
- Choosing organic, paraben and SLS free personal hygiene and cleaning products
- Avoiding smoking, including passive smoking and recreational drugs
- Choosing organic produce where possible
- Minimise consumption of large fish such as swordfish and tuna, which are likely to be higher in heavy metals and oceanic contaminants
- Avoiding plastic food and drink containers, particularly soft plastics, and especially avoid microwaving them
Whilst minimising your toxic exposure, ensure a healthy diet that provides a number of key nutrients:
- Including a good number of antioxidants such as zinc, selenium, vitamin C, beta-carotene, vitamin E, flavonoids, and polyphenols – these will help quench any free radicals created during detoxification. You can achieve a broad range of antioxidants by consuming a “rainbow” of fruit and vegetables
- Increasing consumption of cruciferous and brassica vegetables, as well as onion, garlic, and leek to support Phase 2 liver detoxification and healthy hormonal clearance
- Reduce consumption of caffeine, refined sugars, food additives and alcohol
It is also important to support healthy bowel motility to prevent reabsorption of toxins and hormones in the digestive tract.
Ensure you include a diverse range of plant foods for their prebiotic properties, which can support diversity in the gut microbiome and healthy bowel movements. Onions, chicory, pomegranate, olives, baked apples and Jerusalem artichokes are particularly rich sources of prebiotics.
Herbs that support liver function
Botanical formulations have a long history of traditional use to support and protect the liver. They do so via a number of mechanisms including regeneration of liver cells, enhancing bile production and flow, upregulating detoxification pathways and providing antioxidant support.
The following have been shown in studies to support liver health:
Dandelion (Taraxacum officinale)11
- Source of hepatoprotective polyphenols
- Shown to have antioxidant capabilities by scavenging reactive oxygen species and reactive nitrogen species
- Considered a bitter, which are used to support digestion, in particular where sluggish liver or gallbladder are suspected
Turmeric12 (curcuma longa)
- Shown to supress proinflammatory cytokines and lipid peroxidation products
- Polyphenolic free radical scavenger (antioxidant)
- Shown to support phase 2 pathways
Shizandra13 (Schisandra chinensis)
- Studies suggest may attenuate liver steatosis and inflammation
Cynara (Cynara scolymus)14
- Supports antioxidant function, studies showed an increase in superoxide dismutase, catalase, glutathione, and glutathione peroxidase levels
- Considered a bitter, which are used to support digestion, in particular where sluggish liver or gallbladder are suspected
Burdock (Arctium lappa)15
- Enhances antioxidant enzyme activities and total antioxidant capacity
- May serve as a potential therapeutic compound against both acute inflammation and various chronic diseases
Silymarin (silybum marianum)
- High flavonoid content
- Empirical, historical use for liver support
- Liver detoxification involves 2 phases. Phase 1 converts lipid soluble toxins into water soluble toxins. In doing so these become highly oxidative and therefore damaging, known as reactive oxygen intermediates. Phase 2 combines another molecule with the toxin to neutralise it and allow it to be excreted; this is known as conjugation.
- If phase 2 is not functioning as actively as phase 1 it can lead to an imbalance and create high amounts of oxidative stress in the liver, which can lead to liver damage and dysfunction.
- Antioxidants are essential for supporting liver health in order to reduce damage by reactive oxygen metabolites.
- The gut and the liver are closely related as the gut will produce and absorb toxins that the liver must metabolise; the liver will place detoxified products into the gut for excretion. Therefore, the gut and liver should be supported together.
- Supporting the liver involves reducing exposure to environmental toxins by choosing organic foods and cosmetics, quitting smoking and reducing alcohol content. It is also important to ensure adequate intake of all nutrients as many contribute to liver function but also provide antioxidant support particular with nutrients such as glutathione, N-acetyl cysteine, vitamin C and selenium.
- A number of herbal ingredients have a long history of safe and traditional use for supporting liver health, including milk thistle, dandelion, curcumin, burdock and artichoke.
- Bland J et al. Textbook of Functional Medicine.; 2008.
- Hodges RE, Minich DM. Modulation of Metabolic Detoxification Pathways Using Foods and Food-Derived Components: A Scientific Review with Clinical Application. J Nutr Metab. 2015;2015. doi:10.1155/2015/760689
- Li S, Li H, Xu X, Saw PE, Zhang L. Nanocarrier-mediated antioxidant delivery for liver diseases. Theranostics. 2020;10(3):1262-1280. doi:10.7150/THNO.38834
- DeLeve LD, Kaplowitz N. Glutathione metabolism and its role in hepatotoxicity. Pharmacol Ther. 1991;52(3):287-305. doi:10.1016/0163-7258(91)90029-L
- Casas-Grajales S, Muriel P. Antioxidants in liver health. World J Gastrointest Pharmacol Ther. 2015;6(3):59-72. doi:10.4292/wjgpt.v6.i3.59
- Li S, Tan HY, Wang N, et al. The role of oxidative stress and antioxidants in liver diseases. Int J Mol Sci. 2015;16(11):26087-26124. doi:10.3390/ijms161125942
- Milosevic I, Vujovic A, Barac A, et al. Gut-Liver Axis, Gut Microbiota, and Its Modulation in the Management of Liver Diseases: A Review of the Literature. Int J Mol Sci. 2019;20(2):395. doi:10.3390/IJMS20020395
- Baker JM, Al-Nakkash L, Herbst-Kralovetz MM. Estrogen-gut microbiome axis: Physiological and clinical implications. Maturitas. 2017;103:45-53. doi:10.1016/J.MATURITAS.2017.06.025
- Ervin SM, Li H, Lim L, et al. Gut microbial β-glucuronidases reactivate estrogens as components of the estrobolome that reactivate estrogens. J Biol Chem. 2019;294(49):18586-18599. doi:10.1074/JBC.RA119.010950
- Byrne CD, Targher G. NAFLD: A multisystem disease. Published online 2015. doi:10.1016/j.jhep.2014.12.012
- Colle D, Arantes LP, Gubert P, et al. Antioxidant Properties of Taraxacum officinale Leaf Extract Are Involved in the Protective Effect Against Hepatoxicity Induced by Acetaminophen in Mice. https://home.liebertpub.com/jmf. 2012;15(6):549-556. doi:10.1089/JMF.2011.0282
- Farzaei MH, Zobeiri M, Parvizi F, et al. Curcumin in Liver Diseases: A Systematic Review of the Cellular Mechanisms of Oxidative Stress and Clinical Perspective. Nutrients. 2018;10(7):855. doi:10.3390/NU10070855
- Li Z, He X, Liu F, Wang J, Feng J. A review of polysaccharides from Schisandra chinensis and Schisandra sphenanthera: Properties, functions and applications. Carbohydr Polym. 2018;184:178-190. doi:10.1016/J.CARBPOL.2017.12.058
- Salekzamani S, Ebrahimi-Mameghani M, Rezazadeh K. The antioxidant activity of artichoke (Cynara scolymus): A systematic review and meta-analysis of animal studies. Phytotherapy Research. 2019;33(1):55-71. doi:10.1002/PTR.6213
- Liu W, Wang J, Zhang Z, et al. In vitro and in vivo antioxidant activity of a fructan from the roots of Arctium lappa L. Int J Biol Macromol. 2014;65:446-453. doi:10.1016/J.IJBIOMAC.2014.01.062
If you have any questions regarding the health topics that have been raised, please don’t hesitate to get in touch with our nutritionist team via e-mail or phone:
Last updated on 27th September 2023 by cytoffice