Phase 1 & 2 Liver Detoxification

Phase 1 2 detox

Toxic chemicals that enter the body are fat-soluble, which means they dissolve only in fatty or oily solutions & not in water, making them difficult for the body to excrete.

 

Inside the liver cells there are sophisticated mechanisms that have evolved over millions of years to break down toxic substances. Every drug, artificial chemical, pesticide and hormone, is broken down (metabolised) by enzyme pathways inside the liver cells. Fat soluble chemicals have a high affinity for fat tissues and cell membranes, which are made of fatty substances. In these fatty parts of the body, toxins may be stored for years, being released during times of exercise, stress or fasting.

During the release of these toxins, symptoms such as headaches, poor memory, stomach pain, nausea, fatigue, dizziness and palpitations may occur. The body's primary defence against metabolic poisoning is carried out by the liver. The liver has two mechanisms designed to convert fat-soluble chemicals into water soluble chemicals so that they may then be easily excreted from the body via watery fluids such as bile and urine.

How the Liver Detoxifies

There are two major detoxification pathways inside the liver cells, which are called the Phase 1 and Phase 2 detoxification pathways.

Toxin list

  • metabolic end products
  • micro organisms
  • contaminants/pollutants
  • insecticides
  • pesticides
  • food additives
  • drugs
  • alcohol

Phase One - Detoxification Pathway

Phase one detoxification consists of oxidation reduction and hydrolysis. Phase one detoxification is catalysed by enzymes referred to as the cytochrome P450 enzyme group or Mixed Function Oxidase enzymes MFO. These enzymes reside on the membrane system of the liver cells (called Hepatocytes). Human liver cells possess the genetic code for many isoenzymes of P-450 whose synthesis can be induced upon exposure to specific chemicals. This provides a mechanism of protection from a wide variety of toxic chemicals.

To put it simply, this pathway converts a toxic chemical into a less harmful chemical. This is achieved by various chemical reactions (such as oxidation, reduction and hydrolysis), and during this process free radicals are produced which, if excessive, can damage the liver cells. Antioxidants (such as vitamin C and E and natural carotenoids) reduce the damage caused by these free radicals. If antioxidants are lacking and toxin exposure is high, toxic chemicals become far more dangerous.

Some may be converted from relatively harmless substances into potentially carcinogenic substances. Excessive amounts of toxic chemicals such as pesticides can disrupt the P-450 enzyme system by causing over activity or what is called 'induction' of this pathway. This will result in high levels of damaging free radicals being produced. The danger is if these reactive molecules are not further metabolised by Phase II conjugation, they may cause damage to proteins, RNA, and DNA within the cell.

Substances that may cause overactivity (or induction) of the P- 450 enzymes

  • Caffeine
  • Alcohol
  • Dioxin
  • Saturated fats
  • Organophosphorus pesticides
  • Paint fumes
  • Sulphonamides
  • Exhaust fumes
  • Barbiturates

The family of P-450 enzyme systems is quite diverse, with specific enzyme systems being inducible by particular drugs, toxins or metabolites. It is this characteristic that has allowed the development of special tests to check the function of the various pathways.

The Substrates (the substance acted upon by the enzyme) of cytochrome P-450 enzymes.

  • Theophylline
  • caffeine
  • phenacetin
  • acetaminophen
  • Lidocaine
  • erythromycin
  • cyclosporin
  • ketoconazole
  • testosterone
  • estradiol
  • cortisone
  • Alprenolol
  • bopindolol
  • carvedilol
  • metoprolol
  • propranolol
  • Amitriptyline
  • clomipramine
  • desipramine
  • nortriptyline
  • Codeine
  • dextrometh- orphan
  • ethylmorphine
  • 4-methoxyamphetamin
  • Phenytoin
  • ibuprofen
  • naproxen
  • oxicam drugs
  • S-warfarin
  • Diazepam
  • hexobarbitone
  • imipramine
  • omeprazole
  • alcohol
  • chlorzoxazone
  • enflurane

Cofactors of P450 Phase 1 detoxification

NADH, riboflavin, niacin, magnesium, iron, certain indoles from cruciferous vegetables.

Substances that inhibit cytochrome P450

Many substances inhibit cytochrome P450. This situation can cause substantial problems as it makes toxins potentially more damaging because they remain in the body longer before detoxification.

Grapefruit

Grapefruit juice decreases the rate of elimination of drugs from the blood and has been found to substantially alter their clinical activity and toxicity. Eight ounces of grapefruit juice contains enough of the flavonoid naringenin to decrease cytochrome P450 activity by a remarkable 30%.

Curcumin

Curcumin, the compound that gives turmeric its yellow colour, is interesting because it inhibits phase I while stimulating phase II. This effect can be very useful in preventing certain types of cancer. Curcumin has been found to inhibit carcinogens, such as benzopyrene (found in grilled meat), from inducing cancer in several animal models. It appears that the curcumin exerts its anti-carcinogenic activity by lowering the activation of carcinogens while increasing the detoxification of those that are activated. Curcumin has also been shown to directly inhibit the growth of cancer cells. As most of the cancer-inducing chemicals in cigarette smoke are only carcinogenic during the period between activation by phase I and final detoxification by phase II, curcumin in the turmeric can help prevent the cancer-causing effects of tobacco.

Phase I detoxification and ageing

The activity of phase I detoxification enzymes decreases in old age. Aging also decreases blood flow through the liver, further aggravating the problem. Lack of the physical activity necessary for good circulation, combined with the poor nutrition commonly seen in the elderly, add up to a significant impairment of detoxification capacity, which is typically found in ageing individuals.

Phase Two - Detoxification Pathway

This is called the conjugation pathway, whereby the liver cells add another substance (eg. cysteine, glycine or a sulphur molecule) to a toxic chemical or drug, to render it less harmful. This makes the toxin or drug water-soluble, so it can then be excreted from the body via watery fluids such as bile or urine.

Major Phase II pathways

  • Glutathione
  • Sulphate
  • Glycine
  • Glucuronide conjugations

Through conjugation, the liver is able to turn drugs, hormones and various toxins into water soluble excretable substances. Individual xenobiotics and metabolites usually follow one or two distinct pathways. This makes testing of the various pathways possible by challenging with known substances.

Sulphur containing foods and amino acids stimulate phase II detoxification

For efficient phase two detoxification, the liver cells require sulphur-containing amino acids such as taurine and cysteine. The nutrients glycine, glutamine, choline and inositol are also required for efficient phase two detoxification.

Eggs and cruciferous vegetables (eg. broccoli, cabbage, Brussels sprouts, cauliflower), raw garlic, onions, leeks and shallots are all good sources of natural sulphur compounds to enhance phase two detoxification. Thus, these foods can be considered to have a cleansing action.

The phase two enzyme systems include both UDP-glucuronyl transferase (GT) and glutathione-S-transferase (GSH-T).

Glutathione-S-transferase

Glutathione-S-transferase is the most powerful internal antioxidant and liver protector. It can be depleted by large amounts of toxins and/or drugs passing through the liver, as well as starvation or fasting. Phase II reactions may follow Phase I for some molecules or act directly on the toxin or metabolite.

Substrates of the glycine pathway

Salicylates and benzoates are detoxified primarily through glycination. Benzoate is present in many food substances and is widely used as a food preservative. Many other substances are detoxified as well via the glycine conjugation pathway. Patients suffering from xenobiotic overloads and environmental toxicity may not have sufficient amounts of glycine to cope with the amount of toxins they are carrying.

Substrates of the sulphation pathways

Neurotransmitters, steroid hormones, certain drugs such as Acetaminophen (also known as paracetamol) and many xenobiotic and phenolic compounds.

Substrates of glucuronidation

Polycyclic aromatic hydrocarbons, steroid hormones, some nitrosamines, heterocyclic amines, some fungal toxins, and aromatic amines. It also removes "used" hormones, such as oestrogen and T4 (thyroid hormone) that are produced naturally by the body.

phase 1 and 2 detox

Toxic Overload

If the phase one and two detoxification pathways become overloaded, there will be a build up of toxins in the body. Many of these toxins are fat soluble and incorporate themselves into fatty parts of the body where they may stay for years, if not for a lifetime. The brain and the endocrine (hormonal) glands are fatty organs, and are common sites for fat-soluble toxins to accumulate. This may result in symptoms of brain dysfunction and hormonal imbalances, such as infertility, breast pain, menstrual disturbances, adrenal gland exhaustion and early menopause. Many of these chemicals (eg. pesticides, petrochemicals) are carcinogenic and have been implicated in the rising incidence of many cancers.

Bitter herbs to improve phase 1 and 2 detoxification

Bitter herbs are the corner stone of herbal medicine. A range of physiological responses occur following stimulation of the bitter receptors of the tongue. The bitter taste stimulates the specific bitter taste buds at the back of the tongue to stimulate the parasympathetic nervous system to trigger a number of reflexes. These reflexes are important to the digestive process and general health.

Specifically in relation to digestion herbal bitters;

Sialogogues – stimulate saliva to digest carbohydrates.

Orexogenics – stimulate hydrochloric acid to digest protein.

Chologogues – Stimulate bile flow to digest fats.

The stimulation of the flow of digestive juices from the exocrine glands of mouth, stomach, pancreas, duodenum and liver, aid in digestion, absorption and assimilation of foods and nutrients. There is also a very mild stimulation of endocrine activities, especially insulin and glucagon secretion by the Islets of Langerhans in the pancreas therefore used to treat of non-insulin dependent diabetes. By promoting the flow of bile, bitters assists the liver in its detoxifying capacity.

Herbal medicine to support Liver Detox pathways

Herbs are Nature's vitamins and minerals. You don't need synthetic supplements when you can take organic practitioner strength herbs

Carahealth Heavy Metal & Plastic Detox

Burdock Arctium lappa, Horsetail Equisetum arvense, Milk thistle Silybum marinarum, Alfalfa Medicago sativa

Traditionally indicated to chelate heavy metals

Heavy metals are toxic to the human body and exposures are very common. We can become exposed through water, vaccinations, dental fillings, cosmetics and other personal care products, paint, foods and air pollution. There is strong epidemiological evidence that refutes links between environmental triggers, in particular thimerosal containing vaccines, and the onset of autistic symptoms. The symptoms of toxic heavy metal poisoning and the symptoms of autism, PDD, Aspergers, & ADD/ ADHD are very similar. Toxic metals could be the cause of those symptoms. Memory loss, increased allergic reactions, high blood pressure, depression, mood swings, irritability, poor concentration, aggressive behaviour, sleep disabilities, fatigue, speech disorders, high blood pressure, cholesterol, triglycerides, vascular occlusion, neuropathy, autoimmune diseases, cancer, thyroid disorders and chronic fatigue are just some of the many conditions resulting from exposure to toxins.

Chelation therapy is the administration of chelating agents to remove heavy metals from the body. The most common forms of heavy metal intoxication are those involving lead, arsenic or mercury. There are many products that chelate heavy metals from the body. This tincture contains herbs that are naturally high in minerals which oppose and eliminate heavy metals from the body combines with liver herbs as the liver and the bowel are responsible for the elimination of the heavy metals. It is very important to increase fibre in the diet as fibre “grabs” heavy metals and helps eliminate them from the body. I would recommend taking the herbs for one month.

Diseases associated with heavy metal toxicity include;

Autism
Aspergers
ADD/ ADHD
Memory loss
Increased allergic reactions
Depression
Mood swings
Irritability
Poor concentration
Aggressive behaviour
Sleep disabilities
Fatigue
Speech disorders
High blood pressure
High cholesterol
Triglycerides
Vascular occlusion
Neuropathy
Autoimmune diseases
Cancer
Thyroid disorders
Chronic fatigue syndrome
Fibromyalgia

Carahealth Liver Tonic

Milk thistle Silybum marinarum, Bupleurum/Chai Hu柴胡 Bupleurum falcatum, Globe artichoke Cynara scolymus, Barberry Berberis vulgaris

Traditional Indications

Hepatitis, alcoholism & cirrhosis
Detoxification
Heavy metal toxicity
High cholesterol
Irritably
Melancholia
Nausea
The tincture contains herbs that regenerate liver cells, promote the flow of bile and assist liver functions in particular, digestion and detoxification. It is recommended for liverish conditions such as irritably, melancholia, nausea, feeling sluggish and particular disorders of the liver. This tincture is designed to assist the liver function.

The liver plays a major role in metabolism and has a number of functions in the body, including;

Glycogen storage
Decomposition of red blood cells
Plasma protein synthesis
Hormone production
Detoxification
Bile production (an alkaline compound which aids in digestion, via the emulsification of lipids)


The tincture treats liver diseases such as hepatitis, cirrhosis, alcoholism, haemochromatosis, cancer of the liver, Wilson's disease, autoimmune disease of small bile ducts, Budd-Chiari syndrome, obstruction of the hepatic vein and Gilbert's syndrome and assists detoxification, especially of heavy metals.

For further details on this topic, to lecture for your group or institution on this subject. or to arrange an online appointment contact Carina This email address is being protected from spambots. You need JavaScript enabled to view it.

Carina Harkin BHSc.Nat.BHSc.Hom.BHSc.Acu.

Cert IV TAE. ARCHTI mem.