The liver is one of the most vital organs in the human body, responsible for detoxification, metabolism, and nutrient storage. Understanding how liver detoxification works and how to support it is crucial for optimal health. This article dives deep into the science of liver detoxification, exploring its mechanisms, supporting factors, and practical strategies to enhance its function.

Basics of the Liver

The liver is located in the top right corner of the abdominal cavity, immediately below the diaphragm, to the right of the stomach. Below the liver is the gallbladder. Compared to other internal organs, the liver has a double blood supply via the portal vein and the hepatic arteries, indicating its importance to the entire system. The liver is also a sizeable organ—it weighs an average of 1.5 kg. More than 2,000 liters of blood flow through it every day.

The liver also contains the bile duct system, which collects the bile produced by the liver. Bile ducts generally refer to all ducts through which bile travels from the liver to the gallbladder and duodenum.

Main functions of the liver:(1)

• Carbohydrate metabolism:
  • Produces glucose from amino acids, lactic acid and glycerol
  • Breaks down glycogen into glucose
  • Forms glycogen from glucose
• Fat metabolism:
  • Oxidizes fatty acids into energy
  • Produces large amounts of cholesterol, phospholipids and lipoproteins (such as LDL, HDL, VLDL)
• Protein metabolism:
  • Breaks down amino acids
  • Converts toxic ammonia into urea (urea cycle)
  • Produces blood plasma proteins (including albumin)
  • Produces amino acids and converts them into other compounds
• Bile secretion
• Production of red blood cells and coagulation agents
• Storing glucose (glycogen), fat-soluble vitamins (A, D, K) and vitamin B12, iron and copper
• Cleaning and defense functions:
  • Breaks down several hormones (including insulin)
  • Breaks down and neutralizes toxins (detoxification)
  • Removes (through urine) bilirubin released by red blood cells

Liver diseases are on the rise 

Liver disease-related mortality rates tripled between 1970 and 2010.(2) Today's stressful work culture, alcohol use, problematic diet, and other environmental stressors have led to impaired liver function in many individuals.(3) Abdominal obesity, in particular, contributes to the development of fatty liver disease.(4) It has been estimated that a waist circumference exceeding 100 cm in men and 90 cm in women is a highly likely indicator of fatty liver disease.(5) Recommended waist circumference figures are less than 94 cm for men and less than 80 cm for women. Approximately 80 % of individuals with a BMI over 30 have fatty liver disease. The most precise method of diagnosing fatty liver disease is by liver biopsy.(6)

To determine the presence of non-alcoholic fatty liver disease (NAFLD), the so-called fatty liver index (FLI) can be utilized, factoring in the body mass index (BMI), waist circumference, blood triglyceride levels and gamma-glutamyl transferase (GGT) levels.

The formula used to calculate FLI:

FLI = [e0.953 × ln (TG) + 0.139 × BMI + 0.718 × ln (GGT) + 0.053 × WC - 15.745/(1 + e0.953 × ln (TG) + 0.139 × BMI + 0.718 × ln (GGT) + 0.053 × WC - 15.745)] × 100

• TG = Triglyceride in blood (mg/dL)
• BMI = Body mass index
• GGT = Gamma-glutamyl transferase in blood (U/I)
• WC = Waist circumference (cm)

Scientists have determined the following cut-off points for fatty liver disease: for men, 46.9 or greater; for women, 53.8 or greater. In practice, a value of less than 30 rules out fatty liver disease, whereas a value over 60 is a specific indicator of the disease.(7) The higher FLI value in women is thought to be due to the liver-protecting effect of estrogen.(8) 

According to a comprehensive review, FLI is the most precise tool for the non-invasive assessment of fatty liver disease. However, simply measuring the waist circumference is nearly as accurate in determining non-alcoholic fatty liver disease.(9)

Various medications also have a significant role in the development of liver damage. More than 900 drugs have been reported to cause liver damage. Various medications cause one-half of all acute cases of liver failure.(10) Some medicinal herbal products may also be harmful to the liver.(11)

The liver has an astonishing ability to regenerate. Indeed, it is the only internal organ that can. Even when 75 % of the liver has been destroyed, it may return to normal.(12) Liver function can be supported through nutrition. This involves supporting the cytochrome P450 enzyme system, which is central to the liver detoxification function. The system consists of two distinct phases (1 and 2). Both phases must run smoothly to maintain the optimal liver detoxification function.(13)

The Liver's Role in Detoxification

The liver detoxifies harmful substances through a two-phase process known as Phase I and Phase II detoxification. These phases cooperate to neutralize toxins, making them water-soluble for excretion via urine or bile.(14)

Phase I Detoxification: Oxidation, Reduction, and Hydrolysis

• Enzymes Involved: Cytochrome P450 enzymes (CYP450) are the primary catalysts in Phase I.
• Process: Toxins are transformed into intermediate metabolites, often more reactive and potentially harmful than the original compounds.
• Supporting Nutrients:
  • B vitamins (especially B2, B3, B6, and B9)
  • Antioxidants (vitamin C, vitamin E, glutathione)
  • Flavonoids (quercetin, resveratrol)

Phase II Detoxification: Conjugation

• Process: Intermediate metabolites from Phase I are conjugated with molecules like glutathione, sulfate, or glycine, making them water-soluble and less toxic.
• Pathways:
  • Glutathione conjugation
  • Sulfation
  • Methylation
  • Acetylation
• Supporting Nutrients:
  • Sulfur-containing amino acids (cysteine, methionine)
  • Magnesium
  • Selenium
  • N-acetylcysteine (NAC)

Key Biomarkers for Liver Health

Monitoring liver function through biomarkers is essential for assessing detoxification capacity. Key biomarkers include:

Biomarker	Function	Normal Range
ALT (Alanine Aminotransferase)	Indicates liver cell damage	7–56 U/L (under 25 is optimal)
AST (Aspartate Aminotransferase)	Reflects liver and muscle health	10–40 U/L (under 25 is optimal)
GGT (Gamma-Glutamyl Transferase)	Sensitive marker for bile duct issues and alcohol consumption	9–48 U/L (under 35 is optimal)
Bilirubin	Measures bile production and liver’s ability to process waste	0.1–1.2 mg/dL
Albumin	Reflects liver’s protein synthesis capacity	3.5–5.0 g/dL

 

Alanine Aminotransferase (ALT)

Alanine aminotransferase (ALT) is an enzyme found most commonly in hepatocytes (the liver) and, to a lesser extent, the kidneys. Alanine aminotransferase also occurs in muscle cells, adipose tissue, the

brain, and the prostate. The ALT enzyme catalyzes the transfer of amino groups from L-alanine to alpha-ketoglutarate, producing L-glutamate and pyruvate. This chemical process is crucial for the mitochondrial citric acid cycle.(15) Elevated ALT levels usually indicate liver damage caused by various illnesses – as liver cells are damaged, alanine aminotransferase is released into the circulation. The ALT levels in hepatocytes are 3,000 times higher than in the blood.(16)

ALT levels may also be elevated due to heavy exercise (for up to a week afterward),(17) alcohol use, hepatitis, celiac disease, certain medications (such as Paracetamol, statins, and opiate-based analgesics), and severe burns.(18) Moderate increases in ALT levels also occur in connection with metabolic disorders such as hyperlipidemia, obesity, and type 2 diabetes. 

In many countries, the ALT levels are used to support the diagnosis of metabolic syndrome.(19-20) An increase in the ALT levels is directly proportional to the occurrence and severity of metabolic syndrome – the higher the ALT levels, the more likely and severe the metabolic syndrome.(21)

Extremely high ALT levels (10x the normal level) are usually caused by acute hepatitis. Elevated ALT levels are linked to increased mortality. Low ALT levels (below 10) are linked to higher mortality, particularly in the elderly. Low ALT levels may also occur in connection with impaired liver function.(22)

Lifestyle factors decreasing ALT levels include:

• Weight loss, if the individual is overweight(23)
• A hypocaloric diet (with a weight loss intent) in combination with cold-pressed olive oil will quickly reduce ALT levels in individuals with non-alcoholic fatty liver disease (NAFLD)(24)
• Relatively low-carbohydrate (below 35 % / “Mediterranean”) diet(25-26)
  • Reduces ALT levels regardless of whether weight loss occurs
• A gluten-free diet (particularly for individuals with undiagnosed and/or untreated celiac disease)(27-29)
  • A person with celiac disease whose liver function levels (incl. ALT) are elevated will often find that these levels become normalized after a few months of consuming a gluten-free diet
• Physical exercise (moderate intensity)(30-31)
  • Walking and basic aerobic exercise (particularly for individuals with non-alcoholic fatty liver disease or non-alcoholic steatohepatitis [NASH])(32)
  • Moderate-intensity strength training
• Coffee (and caffeine) may inhibit the rise of ALT levels to some extent (more than 2 cups per day vs. no coffee)(33-34)
• Carotenoids from food reduce fatty liver disease and ALT levels(35)
  • For example, beta-cryptoxanthin and, astaxanthin, and other carotenoids
• Vitamin E as a dietary supplement, particularly for individuals with advanced fatty liver disease and slightly elevated ALT levels,(36) as well as individuals with NAFLD, NASH, or CHC (chronic hepatitis C)(37)
• Resveratrol (500 mg/day) as a dietary supplement, particularly for individuals with advanced fatty liver disease(38-39)
• Powdered turmeric (3 g/day)(40)
• N-acetylcysteine (NAC; 600 mg x2/day), particularly for individuals with non-alcoholic fatty liver disease(41)
• Alpha lipoic acid (400 mg/day) and ursodeoxycholic acid (300 mg/day), particularly for individuals with non-alcoholic fatty liver disease(42)
• Artichoke leaf extract (2,700 mg/day) as a dietary supplement, particularly for individuals with steatohepatitis(43) or NAFLD(44)
  • Artichoke leaf extract may also improve blood cholesterol levels (see above)(45)
• Probiotic therapy may reduce liver enzyme levels across the board and promote recovery from non-alcoholic fatty liver disease(46)
  • The mechanisms include reducing harmful bacteria, reducing small intestinal bacterial overgrowth (SIBO), regeneration of the intestinal lining, and immune system regulation

NB! ALT values may have significant biological variation depending on the day and the situation. Any elevated values should, therefore, be monitored with repeat tests, ideally at an interval of a few weeks.(47)

Aspartate Aminotransferase (AST)

Aspartate aminotransferase (AST) is an enzyme found mainly in the liver and the heart, muscle cells, red blood cells, pancreas, kidneys, and the brain. There are two genetically distinct AST isoenzymes: mitochondrial AST (mAST) and cytosolic AST (cAST).(48) Aspartate aminotransferase is important in amino acid and fatty acid metabolism. The AST enzyme catalyzes the transfer of amino groups from aspartate and alpha-ketoglutarate, producing oxaloacetate and glutamate. The chemical

reaction also works in the opposite direction. Oxaloacetate has a crucial role in mitochondrial energy production (citric acid cycle), urea cycle, and the breakdown and formation of glucose. The reaction mentioned above requires bioactive vitamin B6 (pyridoxal-5-phosphate) as a cofactor.(49-51)

AST levels increase in connection with cell damage. Due to this, AST is used to assess damage to the liver or cardiac muscle (cardiac muscle damage is now predominantly assessed using various troponins, usually troponin-T).(52) AST levels can also increase due to certain medications (Paracetamol and statins),(53-54) chemotherapy,(55) heavy exercise and rhabdomyolysis, or acute pancreatitis or cardiac arrest.(56)

Low AST levels sometimes occur in connection with vitamin B6 deficiency.(57) AST may also be elevated in connection with cholestasis (bile duct obstruction) or various liver tumors and cancers. Acute viral hepatitis often causes AST levels to be 10 times higher compared to normal.(58)

Elevated AST levels may also be a risk factor for future type 2 diabetes. This is particularly true if ALT levels are also elevated.(59) Normal-weight individuals with insulin resistance often have elevated ALT levels but not AST. The AST/ALT ratio is under 1.(60)

The AST/ALT ratio (De Ritis ratio)(61) can be used to analyze an increase in AST levels—if the ratio is high, the increase is usually caused by tissues outside the liver. Usually, the AST/ALT ratio is slightly above 1. The highest ratio (above 2) usually involves alcoholic hepatitis. Viral, drug-induced, or autoimmune hepatitis involves an AST/ALT ratio below 1.(62)

Nutritional factors decreasing AST levels include:

• Heavy coffee consumption (≥ 3 cups per day) is linked to lower AST levels, regardless of the caffeine content(63)
• Silymarin extract (milk thistle; 200 mg x 3/day), particularly for individuals with type 2 diabetes(64)
  • Silymarin may repair liver damage and is generally well-tolerated(65-66)
• Green tea extract (500 mg/day), particularly for individuals with non-alcoholic fatty liver disease(67-68)
• A comprehensive meta-analysis on rat and human tests suggests that curcumin extract (dosage
  • ≥ 1,000 mg/day) protects the liver from damage and reduces AST levels(69-70)
• Powdered turmeric (3 g/day)(71)
• Alpha lipoic acid (400 mg/day) and ursodeoxycholic acid (300 mg/day), particularly for individuals with non-alcoholic fatty liver disease(72)
• Alpha lipoic acid (1,200 mg/day) reduces ALT and AST levels in obese individuals with NAFLD(73)

Gamma-Glutamyl Transferase (GGT)

Gamma-glutamyl transferase (GGT) is an enzyme found mainly in the liver but also in the kidneys, pancreas, and intestine. The primary function of GGT is the breakdown and recycling of glutathione. GGT is also involved in the breakdown of many drugs and toxins, the formation of amino acids, and the conversion of inflammatory molecules into other molecules.(74-76)

Elevated GGT levels occur predominantly in connection with liver diseases (hepatitis or cirrhosis) but also with heart failure, stroke, atherosclerosis, diabetes, anorexia, hyperthyroidism, cancer, or pancreatitis. The most common cause of high GGT values is alcohol abuse. Even small amounts of alcohol can increase GGT levels.(77)

Elevated GGT levels also occur in approximately half of all cases of non-alcoholic fatty liver disease (NAFLD, see above). In such cases, the levels are 2–3 times compared to normal.(78) Many drugs can also increase GGT levels. These include anti-inflammatory drugs (NSAIDs), statins, antibiotics, antifungals, SSRIs, and H2 blockers. Environmental toxins can also increase GGT levels.(79) Elevated GGT levels are linked to increased mortality. Low glutathione levels may also increase GGT levels, indicating that GGT levels indicate cellular level oxidative stress.(80) Low GGT levels typically only occur in connection with familial intrahepatic cholestasis.

Elevated GGT levels are also an independent risk factor for type 2 diabetes (along with ALT),(81) as well as an early predictive marker of atherosclerosis, heart failure, arteriosclerosis, gestational diabetes and various liver diseases.(82)

Alcohol-induced increase in GGT levels may be controlled with carotenoid-based antioxidants such as lycopene, alpha- and beta-carotene, and beta-cryptoxanthin. According to researchers, GGT may be an early sign of oxidative stress in the body.(83) The active form of ubiquinone, Ubiquinol (150 mg/day), significantly reduces oxidative stress and GGT levels.(84)

Factors reducing GGT levels include:

• Reducing alcohol use(85)
• Carotenoids and Ubiquinol (see above)
• Avoiding heavy metals and insecticides as well as other pollutants(86)
• Drinking coffee (particularly for men who use alcohol)(87-88)
• Fish oil (a therapeutic dose, 4 g/day)(89)
• Curcumin and turmeric(90)
• The consumption of vegetables, berries, and fruits is linked to lower GGT levels(91)

Factors That Impair Liver Detoxification (Summary)

Various factors can compromise the liver's ability to detoxify effectively. Below is an expanded explanation of these key contributors:

1. Chronic Stress

• Mechanism: Chronic stress elevates cortisol levels, which can disrupt the activity of liver enzymes, particularly those involved in Phase I and Phase II detoxification.(92)
• Impact: Elevated cortisol may lead to imbalances in detoxification pathways, increasing the production of reactive oxygen species (ROS) and oxidative stress.
• Solution: Stress management techniques such as mindfulness, meditation, and regular physical activity can help regulate cortisol levels and support liver function.

2. Poor Diet

• Mechanism: A diet high in processed foods, refined sugars, and trans fats can overload the liver, impairing its ability to metabolize toxins efficiently.(93-94)
• Impact:
  • Processed foods: Often contain additives and preservatives that require additional detoxification effort.
  • Sugar: Promotes inflammation and fatty liver disease, reducing liver efficiency.
  • Trans fats: Increase oxidative stress and inflammation, further burdening the liver.
• Solution: To support liver health, focus on a whole-food diet rich in antioxidants, fiber, and healthy fats

3. Environmental Toxins

• Mechanism: Exposure to pesticides, heavy metals (e.g., lead, mercury), and environmental pollutants can overwhelm the liver's detoxification capacity.(95)
• Impact: These toxins accumulate in the liver, depleting glutathione and other antioxidants and impairing enzyme function.
• Solution :
  • Minimize exposure by choosing organic produce, using air and water filters, and avoiding contaminated environments.
  • Support detoxification with nutrients like glutathione, selenium, and N-acetylcysteine (NAC).

4. Alcohol and Medications

• Mechanism: Excessive alcohol consumption and overuse of medications (e.g., acetaminophen, antibiotics) can overburden the liver, leading to inflammation and damage.(96)
• Impact:
  • Alcohol: Metabolized into acetaldehyde, a toxic compound that damages liver cells and depletes glutathione.
  • Medications: Many drugs are metabolized by the liver, and overuse can lead to drug-induced liver injury (DILI).
• Solution:
  • Limit alcohol intake to moderate levels or avoid it altogether.
  • Use medications only as prescribed and consider liver-supportive supplements like milk thistle.

5. Oxidative Stress

• Mechanism: Oxidative stress occurs when an imbalance between free radicals and antioxidants leads to cellular damage.
• Impact: Depletes glutathione, the liver's primary antioxidant, impairing its ability to neutralize toxins and protect liver cells.
• Solution:
  • Increase intake of antioxidant-rich foods (e.g., berries, leafy greens, nuts).
  • Supplement with antioxidants like vitamin C, E and alpha-lipoic acid (ALA).

Additional Factors

• Sedentary Lifestyle: Lack of physical activity reduces blood flow to the liver, impairing its function.
• Sleep Deprivation: Poor sleep disrupts cellular repair processes, including those in the liver.
• Gut Dysbiosis: An imbalanced gut microbiome can increase the production of endotoxins, further burdening the liver.

Strategies to Support Liver Detoxification

1. Nutrition for Liver Health

• Cruciferous vegetables: Broccoli, kale, and Brussels sprouts support Phase I and II enzymes.
• Sulfur-rich foods: Garlic, onions, and eggs provide precursors for glutathione.
• Healthy fats: Olive oil, avocados, and nuts support bile production.
• Antioxidant-rich foods: Berries, green tea, and turmeric reduce oxidative stress.

2. Lifestyle Interventions

• Exercise: Enhances blood flow and supports detoxification pathways.
• Hydration: Facilitates toxin excretion through urine.
• Sleep: Essential for cellular repair and regeneration.

3. Targeted Supplementation

Complete lists are shown in each biomarker and in the liver detoxification image.

• Milk thistle (Silymarin): Protects liver cells and enhances glutathione production.
• N-acetylcysteine (NAC): Boosts glutathione levels.
• Alpha-lipoic acid (ALA): Supports antioxidant defense and mitochondrial function.
• B vitamins: Essential for Phase I detoxification.

For a complete liver supporting supplement, we recommend Rohtos Shield.

4. Intermittent Fasting and Caloric Restriction

• Stimulates autophagy, a cellular cleanup process that supports liver health.
• Reduces oxidative stress and enhances mitochondrial efficiency.

Advanced Testing for Liver Detoxification

To assess liver function comprehensively, consider the following:

• Comprehensive Metabolic Panel (CMP): Evaluates liver enzymes, proteins, and electrolytes.
• Organic Acids Test (OAT): Measures metabolic byproducts of detoxification. Such as Metabolomix+.
• Glutathione Levels: Assesses the body's primary antioxidant status.
• Heavy Metal Testing: Identifies toxic burdens that may impair liver function. Such as hair elements heavy metal test.

Conclusion

Liver detoxification is a complex, multi-phase process that relies on proper nutrition, lifestyle, and biochemical balance. Understanding the science behind it and implementing evidence-based strategies is ideal for optimizing function and ensuring health.

The liver's ability to detoxify depends on the seamless coordination of Phase I and Phase II detoxification pathways, supported by key nutrients like B vitamins, glutathione, and sulfur-containing amino acids. Factors such as chronic stress, poor diet, environmental toxins, alcohol, and oxidative stress can impair these pathways, leading to a buildup of harmful substances in the body.

To support liver health, prioritize a whole-food diet rich in antioxidants, fiber, and healthy fats, and incorporate lifestyle practices like regular exercise, stress management, and adequate sleep. Targeted supplementation with milk thistle, N-acetylcysteine (NAC), and alpha-lipoic acid (ALA) can further enhance detoxification capacity.

Regular monitoring of liver biomarkers, such as ALT, AST, and GGT, through comprehensive testing can provide valuable insights into liver function and guide personalized interventions. Taking a proactive approach to liver health can improve detoxification, boost energy levels, enhance immune function, and reduce the risk of chronic diseases.

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