The science of detoxification
First published 2/2/2017
Back in my nutrition student days, circa 2000, I used to jest that it was all uptox-downtox, retox-detox. Primarily because I was still living in Melbourne and hanging with the nicest, if not the wildest people! Our late night antics seemed as though they went for days. A hangover from my former life as a publican desperately trying to understand the concept of balance that people speak of. As a hedonist, this paradigm was as foreign to me as my trip to Zanzibar, however over time and eight years of Byron Bay life, I have found a piece of peace on the continuum that threads polarity.
As the new year rolls away from the holidays in Australia and into routine, wonderful campaigns unfold including FebFast. Recently, the benefits of abstinence came under scrutiny. In particular, the effects of eliminating alcohol for 28 days. Abstinence and fasting are prevalent in so many cultures, especially for the Islamic faith who fast over the ninth month in the Islamic calendar. Ramadan is a period of prayer, fasting, charity-giving and self-accountability for Muslims.
Self-accountability. That’s my point. It is not about fashion plates or fasting to be thin, it’s about contemplation of habit. A month of self-awareness with a health focus is a good thing in my book. I have been doing this since 1994, spurred on by a barman at Gowings Grace Darling who bet that I could not give up alcohol for a month. The prize was two tickets to Massive Attack if I won. I did. Easily. And so began a kind of pilgrimage and here I paint you a proper picture of the biochemical science of your liver and tummy. Are you ready? Pour yourself a San Pell. and let’s go.
Thanks to a few readers who asked, liver detoxification goes like this.
The season of spring heralds renewal and cleansing. In Chinese medicine it represents liver energy and the primary function of the liver is detoxification. Your liver’s job is to cleanse and alter the blood and promote the elimination of toxins, hormones and to facilitate digestion. The liver governs fat metabolism by releasing lipids and associated toxins into the blood for elimination. Circles under the eyes, headaches, weight gain, nausea, mood swings and bad breath are all signs of an overloaded liver. Did you know that if you love your liver a little bit more you’d have greater success losing weight?
The primary function of the liver is detoxification. Your liver’s job is to cleanse and filter the blood and promote the elimination of toxins, hormones and to facilitate digestion. The liver is the organ that governs fat metabolism by releasing lipids (fats) and associated toxins into the blood for elimination. It’s a pretty smart organ as it your only organ that can renew its own cells, called hepatocytes.
The National Liver Foundation explains this succinctly as Hepatocytes are metabolically active cells They are involved in regulation of various biochemical and metabolic functions and are involved in synthesis of various substances in the body. They take up glucose, minerals, and vitamins from portal and systemic blood and store them. Many important substances such as blood clotting factors, transporter proteins, cholesterol, and bile components are synthesized by the hepatocytes. The hepatocytes also regulate blood levels of substances such as cholesterol and glucose, the liver helps maintain body homeostasis.
Functions of the Liver
For liver cell (hepatocytes) regeneration, and is used after exposure to chemical and industrial pollutants or adverse effects from excess alcohol or fat consumption.
To increasing elimination from the body and to enhance circulation to clear toxic substances.
To increase the flow of bile which carries stored fat-soluble toxins and takes them away from the liver to be eliminated.
Antioxidants support detoxification and may also help to decrease some of the side effects of detoxification, such as headache or nausea.
If your liver is not functioning at top capacity, then a build-up of toxins can occur. The first sign of toxin build-up is usually headaches and nausea.
Your liver is also responsible for storing glycogen, which is converted into glucose (blood sugar) in times of need. Your liver can store up to about 24 hours worth of glycogen at any one time.
Ok, so now we understand a little bit more about our clever liver, we can move on to what happens when it self-spas! The liver detoxifies in two phases. You need to understand this and it is quoted in detail below. This is a constantly occurring cycle that doesn’t just happen when you stop drinking beer and quit smoking, It is also a long process over months, if not years to totally detoxify. This is why formal detoxification programs for narcotic addiction take months. You might read in a trashy mag that he/she was in rehab for six months, for example. So you simply cannot do this in a three-day, magazine prescribed detox diet. Gentle cleanse, yes, absolutely. Abstinence, of course, you’ll have more energy and therefore will probably feel like exercising each day and eating well. A five to seven-day trip to a fabulous health retreat will certainly help you get on track, but you will not be completely ‘detoxified’ on your return.
Alcohol, ethanol and acetaldehyde
Ethanol is metabolized into the perilous & toxic hangover causing acetaldehyde mainly by the action of alcohol dehydrogenase in the liver, while mainly by the action of catalase in the brain. Increased liver generation of acetaldehyde leads to increased blood acetaldehyde levels and aversion to ethanol in animals….but not in humans it seems!
Jacquelyn J. Maher M.D. writes
As alcohol is broken down in the liver, a number of potentially dangerous by-products are generated, such as acetaldehyde and highly reactive molecules called free radicals. Perhaps more so than alcohol itself, these products contribute to alcohol-induced liver damage. The liver is one of the largest organs in the body; it has not only considerable reserves but also the ability to regenerate itself. Consequently, symptoms of liver damage may not appear until damage to the organ is quite extensive. Epidemiological studies suggest that a threshold dose of alcohol must be consumed for serious liver injury to become apparent (Mezey et al. 1988).
Most of the alcohol that people drink is metabolized in the liver. The major pathway for alcohol metabolism involves the enzyme alcohol dehydrogenase (ADH). This enzyme converts alcohol to acetaldehyde through a chemical process called oxidation. As alcohol is broken down in the liver, a number of potentially dangerous by-products are generated. Acetaldehyde is highly toxic to the body, even in low concentrations. Normally, however, the enzyme aldehyde dehydrogenase (ALDH) rapidly oxidises acetaldehyde to acetate.
This is why some people are having an “affair with bottle” may have breath that smells like nail polish remover – acetate.
See also My Top Ten Hangover Hacks here
Phase 1 And 2 Liver Detoxification Pathways – by Carahealth
With respect to the author Carina Harkin BHSc.Nat.BHSc.Hom.BHSc.Acu. is a practitioner of 11 years, complementary medicine lecturer of 4 years and mother of six in Galway, Ireland who practices what she teaches. Please see also Carahealth Heavy Metal Detox and Carahealth Liver.
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.
Many of the toxic chemicals that enter the body are fat-soluble, which means they dissolve only in fatty or oily solutions and not in water. This makes them difficult for the body to excrete. 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.
- metabolic end products
- micro organisms
- food additives
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
- Saturated fats
- Organophosphorus pesticides
- Paint fumes
- Exhaust fumes
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.
View the Substrates (the substance acted upon by the enzyme) of cytochrome P-450 enzymes.
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 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, 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
- 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 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.
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.
Read more from Carahealth here