Liver Health and Detoxification System

by Hugo Allen-Stevens

Contents
The importance of the liver
Phase 1 Detoxification
Phase 2 Detoxification
Detoxification pathways
Toxins
Alcohol
Detoxing and weight loss
Fat and Liver health
Aids to detoxification

Detoxification is chiefly performed by the liver. Toxic overload can occur as a result of overloading its capabilities to detoxify, chiefly through intake of toxic chemicals that include:

1. Food additives and colorings
2. Solvents such as cleaning products
3. Pesticides in foods
4. Herbicides in foods (and air)
5. Drugs (illegal, over-the-counter, prescription)
6. Alcohol
7. Naturally occurring toxins in foods and herbs

1

The importance of the liver

Functions:

1. Produce glucose
2. Convert glucose to glycogen for later use
3. Convert fatty acids, amino acids, vitamins and minerals to usable forms
4. Make cellular structural components such as cell membrane compounds (phospholipids), cholesterol, and components that carry these in blood (lipoproteins); break down all these components and recycle them into bile salts
5. Monitor body requirements and converting amino acids into glucose or protein for body function
6. Break down excess amino acids and further break down ammonia into urea (excreted by kidneys
7. Produce important blood proteins, including immune factors, proteins involved in blood clotting, and crucial component of hemoglobin
8. Store Iron, Vit A, D, B12
9. Recycle old blood cells
10. Bile salt production
11. Filter and remove toxins from blood for excretion in urine of in bile

2

Phase 1 Detoxification

• Detoxification enzymes break apart toxic molecules into two or more harmless components
• Toxic molecules are changed so they can be dissolved in water in order to:
  • Circulate the toxin in the blood to the kidneys for excretion in urine
  • Attach the toxin to bile for excretion in faeces
• Transform the molecule into another form for work in phase 2 detoxification

Symptoms of a dysfunctional phase 1:

• Sensitivity to or craving for alcohol
• Caffeine intolerance (indicates underactive phase 1)
• Rapid caffeine metabolism (indicates overactive phase 1)
• Liver disease
• Parkinson’s disease
• Illness resulting from exposure to perfumes or environmental chemicals

During phase 1, many toxins made more active and potentially more damaging – such as if they are oxidized. If there is an inadequate supply of anti-oxidants, free radical damage to tissues can result. Equally, if Phase 2 is under stress or not functioning, substances formed by phase 1 can cause more harm – eg alcohol: phase 1 converts alcohol to acetaldehyde, which is converted in phase 2 to acetic acid. If phase 2 reactions do not occur, that person will be more sensitive to alcohol (ie become alcoholic or suffer damage such as cirrhosis of the liver)

3

Phase 2 Detoxification 

Conjugation – toxin added (“hand-cuffed”) to another molecule so it can either do no harm, or made water soluble for excretion.

Methods

1. Acetylation: Used for antibiotics, such as sulfa drugs. Using acetyl coenzyme A (acetyl CoA). Need Vit B2, B5, C
2. Amino Acid conjugation: This usually dysfunctional for people with chronic conditions, cancer, liver disorders and long term toxin exposure. Primarily uses amino acid glycine. Need sufficient protein.
3. Glucuronidation: Used for many medical drugs, aspirin, mentol, synthetic vanilla, estrogen and other hormones, cigarette smoke, food additives. Using glucuronic acid. Usually works well
4. Glutathione conjugation: Used for heavy metals especially. Changes fat-soluble toxin to water soluble form. Glutathione is a protein made from amino acids methionine and cysteine. Gluathione also an anti-oxidant – important as liver functions produce many free-radicals
5. Methylation: Used for estrogen and other steroid hormones. Using methyl group (carbon atom and 3 hydrogen atoms) usually made from same chemical: S-adenosylmethionine (SAMe). SAMe made from amino acid methionine, and needs: choline, vit B12, Folic acid.
6. Sulfation: main pathway for environmental toxins, microbial products, drugs, alcohol and food additives. Attaches sulphur to make toxin water soluble. Used for stress hormones – so the more stress experienced, the harder this system has to work. Also, increased sulfation inhibits glutathione pathway leading to increased risk of free-radical damage. Symptoms of overload to sulfation system are nervous system problems such as pins and needles in hands and feet. Needs: amino acids methionine and cysteine. Inhibited by excess molybdenum or Vit B6
7. Sulfoxidation: used for sulphur containing toxins in foods and drugs. Uses enzyme sufite oxidase to convert food preservatives and drugs (eg asthma medication) to sulphate for excretion in urine. If there is sensitivity to sulphur containing substances, usually indicates this pathway if faulty

Detoxification requires systems to work in sync – it is a complex balance. Eg Phase 1 must be in synch with Phase 2 or else toxins will not be cleared fast enough and they will start to do damage

Kidneys

• When the liver does not properly detoxify, it leaves the kidneys vulnerable to damage. And if the liver overwhelms the kidneys with excreted matter, this can in turn overwhelm the kidneys and leave them vulnerable to damage.
• Dehydration is a chief concern

4

Detoxification pathways – health problems will deplete nutrients needed for detoxification (such as Glutathione) and reduced nutrients will increase the risk of health problems = vicious cycle

Phase I – oxygen introduced to toxin: to produce “active site”

Phase 1 major reactions involve the oxidation, reduction and hydrolysis of toxins. Nutrients required are: B vitamins, folic acid, Glt, Anti-oxidants: Milk Thistle, Vit E and C. Anti-oxidant protection is crucial to prevent ROS production and damage to immune, endocrine and nervous systems

Phase 2 – conjugation: water soluble substances added to “active site”. Reactions involved are Sulfation, Glutathione Conjugation and amino acid conjugation

Phase 2 conjugation and sulfation: toxins are made water soluble. Required nutrients are:

• Methionine
• Glt
• Glycine: involved in synthesis of Glt and is biotransformed into acids and and amines that are used in Phase 2 reactions
• Taurine: involved in phase 2 detoxification and bile acid conjugation reactions
• Cysteine
• Sulfurated phytonutrients found in garlic and cruciferous veg

Key aminos – Methionine and cysteine

Methionine

• coverted to S-adenosl-L-methionine (SAM or SAMe) with addition of folic acid, Vit B12
• helps produce Glutathione

Glutathione (Glt)

• key ingredient in production in body is cysteine along with glycine and glutamic acid
• most important compound in elimination of fat soluble toxins (heavy metals, solvents, pesticides), transforming them into water soluble form for excretion via kidneys
• the faster the toxic exposure, the faster the body uses Glt
• without Glt cells die faster, leading to faster aging or cells, tissues and organs, enhanced risk of toxin induced disease, and cancer
• people with low levels Glt
  • smokers
  • people chronically exposed to toxins
  • inflammatory condition sufferers (eg rheumatoid arthritis)
  • chronic condition sufferers (eg AIDS, diabetes)
  • health problems
    • these deplete Glt in body
    • low levels Glt lead to increased risk of health problems
    • vicious cycle
  • Glt can be found in asparagus, avocado, walnut (very rich source)
    • Cooking destroys it
    • Vit C helps body to manufacture it as well as boosting blood levels of Glt
    • Co-factors in production in body are: Vit B6, Riboflavin, Selenium

Glutathione is a bioactive amine – a tripeptide amino acid absorbed directly from food or synthesized in the body from the amino acids Cysteine, Glycine and Glutamic Acid. Its roles include:

• Detoxification in the liver
• Anti-oxidant of reactive oxygen species and free radicals
• Regulation of redux balance
• Regulation of prostaglandin metabolism
• Deoxyribonuucleotide synthesis
• Cell proliferation
• Immune messaging

In the liver, Glutathione is needed in Phase II conjugation of toxins – making toxins water soluble prior to excretion via the kidneys. It thus plays a central role in preventing and treating cancer. It is also needed for treating inflammatory conditions (eg Arthritis) and chronic diseases (eg Diabetes), as well as proving useful in treating Parkinson’s disease and preventing blood clots in operations. Health problems will use up Glutathione, and low levels of it lead to increased risk of health problems.

Sulfation

Sulfation occurs when toxicants are converted to water soluble substances prior to excretion in the urine. It occurs as a result of metabolism the sulphur amino acids Cysteine, Homocysteine or Methionine into organic sulphate – a process called “sulphoxidation”. Sulfation may be inhibited due to:

1. Excess exogenous toxicants in the body and diet (ie heavy metals like lead and mercury).
2. Excess sulphites accumulating in the body (resulting from low levels of the mineral molybdenum in the diet, molybedenum being used to produce the enzyme sulphite oxidase, used in sulphite detoxification and conversion into sulphate)
3. Poor control of the steroid sulfotransferase – caused by consumption of red wine, coffee, certain cheeses and chocolate (as well as genetic, environmental and other toxicity factors).
4. Mediating factors causing and being caused by problems in the metabolism of Cysteine:
   1. Motorneuron diseases such as Parkinson’s disease and Alzheimer’s disease
   2. Inflammatory conditions such as rheumatoid arthritis, delayed food sensitivity, multiple chemical sensitivities, and diet-response autism

5

Toxins: exogenous (from outside of body, such as xenobiotics and heavy metals) and endogenous (made inside body, such as hormones, lipids and peptides)

• metabolic end products (endotoxins)
• micro-organisms
• contaminants / pollutants
• insecticides
• pesticides
• food additives
• drugs
• alcohol

Toxins lead to cells dying faster and faster aging, toxin induced disease (eg cancer), Oxygen free radical production that can damage immune, endocrine or nervous system

Toxins are made soluble for excretion in urine or in bile

 

Toxic overload

Detoxification uses 80% of the energy the body uses to make new molecules. Toxic overload results in low energy levels as more energy is being devoted to detoxification, leaving little energy for other body processes

• Continual or repeated damage (eg drugs and alcohol use) interferes with liver’s ability to function (leading to cirrhosis). If the liver slows down, toxins build up
• Heavy metal toxicity – collect inside cells, especially those of brain, nerves, kidney, immune system and disrupt cell function or cause cell dysfunction. Symptoms include: headache, fatigue, tremors, dizziness, lack of coordination, impaired ability to think and concentrate, learning disabilities (ADD), muscle aches, indigestion, constipation, anaemia, high blood pressure. Sources of heavy metals include: environmental contamination; lead in pesticides; solder in tin cans; cadmium and lead from cigarette smoke; mercury from fish or dental fillings; aluminium from cookware, food containers, anti-perspirants and antacids

6

Alcohol

Triggers release of gastric juices. Causes vasodilation. Can cause inflammation and weakening of stomach lining, and increased risk of stomach (gastric) ulcers. Inhibits production of antidiuretic hormone causing mis-regulation of water in blood by kidneys – which can lead to dehydration. Broken down in liver through sulfation pathway – meaning more alcohol puts more pressure on this pathway and too can overwhelm it. It can also do direct damage to liver cell function, resulting in fat accumulation in liver, which results in reduced bile flow, leading to increased build-up of toxins in body / reduced excretion of them

Excess fat, low fiber diets and bile salts

Good detoxification (and digestion) requires adequate supplies of bile from the liver and proper bile flow to gallbladder (and duodenum / intestines). Bile pathway is how liver excretes toxins it has processed. If pathway blocked, toxins will build up in liver. High fat diets and low fiber diets contribute to gallstones or blockages in bile pathway (ducts or gallbladder). Stones form due to excess cholesterol excretion in bile, or problems is suspending it correctly in fatty bile solution. Symptoms include fatigue, malaise, digestive disturbances, allergies and chemical sensitivities, constipation.

7

Detoxing and weight loss

Many toxins are fat soluble and stored in body fat (eg heavy metals). When these cells are broken down, toxins are released in blood, increasing risk of tissue damage (especially to brain and nerves) as well as toxic overload to liver.

Liver needs steady supply of nutrients to keep detoxifying correctly – such as proteins, vitamins, minerals to produce key enzymes and bile. Fiber from whole grains, fruit, vegetables absorb water in body and toxins it contains (such as those secreted by liver in bile salts). Liver excretion in bile is reabsorbed in the intestines – unless fiber is present to absorb those water soluble toxins. Fiber is not absorbed or broken down: it simply adds bulk and water to fecal matter, which lubricates stool, as well as making it pass more quickly and easily out of body – taking toxins with it.

8

Fat and Liver health

Fat in the liver will impair liver function and detoxification. Factors as alcohol consumption (which causes fat to accumulate in liver) or diets high in saturated, damaged or chemically altered fats (amongst other factors) can cause fat to accumulate in the liver.

• Individual fatty acids are grouped for storing after digestion into triglycerides by the liver
• That the liver is producing these storage form lipids
  • indicates excessive dietary intake (symptomatic of obesity and diabetes) of either fat or sugar
  • symptomatic of a sedentary lifestyle
  • symptomatic of excess alcohol consumption (as alcohol damages the liver where these fats are produced as well as prompting production and accumulation of fat in the liver).
• Nutritional support for fat metabolism, preventing fat accumulation and exporting fat from liver:
  • Choline needed to export fat from liver (without it, fat becomes trapped in liver, blocking metabolism): Best sources egg yolk, beef, orange and cauliflower; can be manufactured in body (from methionine and serine)
  • Betaine helps liver process fat and prevent chemical damage, as well assisting in metabolism of homocysteine to methionine: best sources are beets, fish, legumes

9

Aids to detoxification:

1. Botanical – Silymarin / Milk Thistle seed: enhances detoxification reactions and acts as anti-oxidant to protect liver from toxic chemicals and free-radicals (even more potent that Vit C and E in free-radical liver protection)
2. Vegetable – beets and Brassica family vegetables (eg cabbage, broccoli and brussel sprouts)
3. Protein – adequate supply and especially sources for Glutathione (found especially in asparagus, avocados, walnuts, Brassica family plants, and fresh fruits, fish and meat)
4. Phytochemical – Limonene found in citrus fruits, dill and caraway seed all boost the body’s production of glutathione
5. Anti-oxidants

• carotenes (red and yellow fruits, green leafy vegetables, grains and seeds)
• flavonoids (darker fruits, vegetables)
• lignans (flaxseed, whole grains, nuts, seeds)
• polyphenols (green tea, chocolate, red wine)
• Vitamins C and E

Nutrients required for good detoxification

1. For phase 1 detoxification – copper, magnesium, zinc, vitamin C.
2. For acetylation – B vitamins (whole grains), Vitamin C (peppers, cabbage and citrus fruits)
3. For amino acid conjugation – need adequate protein
4. For Glucuronidation – limonene rich foods such as citrus fruits, dill, caraway; and sulphur containing foods
5. For glutathione conjugation – need protein found especially in asparagus, avocados, walnuts, Brassica family plants, and fresh fruits, fish and meat
6. For methylation – folic acid (green leafy vegetables); vitamin B6 (whole grains and legumes); Vitamin B12 (animal products and supplements)
7. For sulfation – sulphur containing foods such as egg yolks, red peppers, garlic, onions, broccoli, brussel sprouts
8. For sulphoxidation – molybdenum (legumes and whole grains) needed for production of enzyme sulphite oxidase
9. For accelerating fat metabolism in liver, prevent its accumulation there, and promote bile flow out of liver – lipotropic agents such as amino acids choline, betaine and methionine
10. For detoxification of xenobiotics eg PCBs, dioxin – Vit A

Nutrient inhibitors:

Grapefruit – contains flavonoid naringen: reduces activity of enzymes needed to break down certain prescription medications.

Adapted from:

Murray, M. (2001). Total body tune-up. Chapter 3: Tuning up your detoxification system (pp. 65 to 101) and Chapter 7: Tuning up your brain, nerves and senses (pp. 235 to 245). New York, N.Y.: Bantam Press

Bland, J., Costarella, L., Levin, B., Liska, D., Lukaczer, D., Schlitz, B., Schmidt, M., Lerman, R., Quinn, S., Jones, D. (2004). Clinical Nutrition: A Functional Approach, Second Edition. Chapter 3: Proteins, amino acids and Detoxification of the liver (pp. 41 to 640). Gig Harbor, WA: The Institute for Functional Medicine.

Marieb, E.N. (2009). The essentials of human anatomy and physiology. San Francisco, C.A.: Pearson Education