Category: the liver

knowing how your liver works can help you live with gilbert’s syndrome, and how you talk to Dr’s

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Bilirubin explained

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Bilirubin explained

All about Bilirubin.

If you’ve been diagnosed with Gilbert’s Syndrome, then you’ve most probably been told that your bilirubin levels were high.  It’s one of the most common ways of determining that a patient has Gilbert’s Syndrome, and usually happens after general blood tests.

But what is Bilirubin, what does it do and will it harm us? 

Bilirubin comes from the blood when blood cells become old, and die.  Hemaglobin, the substance in blood that carries oxygen, is broken down to heme and globin and is passed onto the liver. Bilirubin is formed from the heme part of hemaglobin, and is a bright greenish yellow colour.

The bilirubin is not water soluble when it gets to the liver, and needs an enzyme to become so, then it can be easily passed out of the body.  The water soluble substance now passes through the gall bladder as bile and into the small intestine where it continues to be processed by bacteria in the intestines, and is passed out through the faeces and urination.

This enzyme that makes the bilirubin water soluble is called glucuronyl transferease, known as UGT for short, and is what people with Gilbert’s Syndrome are genetically lacking.  This means that the bilirubin is not ‘conjugated’ or converted so that it can easily leave the body.

The enzyme also uses blood sugar to help in processing bilirubin, which is one reason why missing meals can affect you.  It’s best to ensure you have regular small meals, and cut down on unrefined sugar and carbohydrates like white bread and pasta, so that the amount of enzyme you have can always have a stable supply of blood sugar to do its job.

There is always some bilirubin that is in the blood but this is chemically different from the ‘conjugated’ bilirubin.  GS sufferers however, have a lot more of this ‘unconjugated’ bilirubin because it hasn’t been disposed of as it should through the usual process. It’s the difference between the 2 types that tips off those conducting the lab tests on your blood that you have GS.

When bilirubin builds up in the blood at more than around 2.5mg/dl, then the skin and eyes become discoloured with yellow, otherwise know as jaundice. There are a number of reasons bilirubin builds up in the blood other than the lack of the enzyme, and it’s important to rule those out before diagnosing Gilbert’s Syndrome.  For example the patient’s bile duct could be blocked, or they could have a type of anaemia, or hepatitis.

Drugs can also affect the measurements of bilirubin, and many can increase it such as  steroids, some antibiotics, antimalarials, codeine, diuretics, MAO inhibitors, nicotinic acid, oral contraceptives, and others.  Drugs that decrease bilirubin measurements include barbiturates, caffeine, penicillin and high dose salicylates.

You’re likely to be diagnosed between the age of 10 and 30.  Males are more likely to have Gilbert’s Syndrome than females, and there are some slight differences in the gene depending on racial background.  Many people will not even notice they have it.

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Glucuronidation – where Gilbert’s Syndrome works in your liver

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Glucuronidation
The UGT enzyme (that people with Gilbert’s Syndrome don’t have so much of) works in one particular part of your liver and is responsible for the part (or pathway) of your liver’s processing called ‘glucuronidation’. Glucuronidation happens when toxins are bound to glucuronic acid which is produced by the liver. Chemicals processed by glucuronidation include common opiate based drugs used in pain relief or during surgery  (Liston, H.; Markowitz, J.; Devane, C. (2001). “Drug glucuronidation in clinical psychopharmacology”. Journal of clinical psychopharmacology). Other things that affect glucuronidation include smoking, obesity, age and gender.

You can find a list of drugs affected here: https://en.wikipedia.org/wiki/Glucuronidation#General_influencing_factors

Some herbal supplements may help glucuronidation (Effects of herbal supplements on drug glucuronidation. Review of clinical, animal, and in vitro studies. March 2011 Mohamed ME, Frye RF.Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, Florida 32610, USA.)The use of herbal supplements has increased steadily over the last decade. Recent surveys show that many people who take herbal supplements also take prescription and nonprescription drugs, increasing the risk for potential herb-drug interactions. In vitro and animal studies indicate that cranberry, gingko biloba, grape seed, green tea, hawthorn, milk thistle, noni, soy, St. John’s wort, and valerian are rich in phytochemicals that can modulate UGT enzymes. However, the IN VIVO consequences of these interactions are not well understood. Only three clinical studies have investigated the effects of herbal supplements on drugs cleared primarily through UGT enzymes. The need for further research to determine the clinical consequences of the described interactions is highlighted.

Essential for Glucuronidation are the nutrients L-glutamine, aspartic acid, iron, magnesium, B3 (niacin) and B6. Thyroid should also be adequate. Cruciferous vegetables (cauliflower, cabbage, cress, bok choy, broccoli and similar green leaf vegetables) are helpful. Glucuronidation efficiency can be improved by calcium-d-glucarate. However, you have to start very gradually with the calcium-d-glucarate, and be very consistent.

You can find out more about glucuronidation here https://youarethehealer.org/health-conditions/optizmize-your-health/detox-biotransformation-pathways/glucuronidation/

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Milk Thistle (Sylbum marianum )

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The medicinal use of milk thistle can be traced back to ancient Greece and Rome.  Today researchers around the world have completed more than 300 scientific studies that attest to the benefits of this herb, particularly in the treatment of liver ailments.

Common uses:

  •        Protects liver from toxins, including drugs, poisons and chemicals.
  •        Treats liver disorders such as cirrhosis and hepatitis
  •        Reduces liver damage from excessive alcohol.
  •        Aids in the treatment and prevention of gallstones
  •        Helps to clear psoriasis.

Forms : capsule, tablet, tincture.

What it is.

Know by its botanical name, Silybum marianum, as well as by its main active ingredient, sylmarin, milk thistle is a member of the sunflower family, with purple flowers and milky white leaf veins.  The herb blooms from June to August, and the shiny black seeds used for medicinal purposes are collected at the end of the summer.

What it does.

Milk thistle is one of the most extensively studied and document herbs in use today.  Scientific research continues to validate its healing powers, particularly for the treatment of liver-related disorders.  Most of its effectiveness stems from a complex of three liver-protecting compounds, collectively know as silymarin, which constitutes 4% to 6% of the ripe seeds.

Major benefits.

Among the benefits of milk thistle is its ability to fortify the liver, one of the body’s most important organs.  The liver processes nutrients, including fats and other foods.  In addition it neutralises, or detoxifies many drugs, chemical pollutants and alcohol.  Milk thistle helps to enhance and strengthen the liver by preventing the depletion of glutathione, an amino acid-like compound that is essential to the detoxifying process.  Moreover, studies have shown that it can increase glutathione concentration by up to 35%.  Milk thistle is an effective gatekeeper, limiting the number of toxins which the liver processes at any given time.  The herb is also a powerful antioxidant.  Even more potent than vitamins C and E, it helps to prevent damage from highly reactive free-radical molecules.  It promotes the regeneration of new liver cells which replace old and damaged one.  Milk thistle eases a range of serious liver ailments, including viral infections (hepatitis) and scarring of the liver (cirrhosis).  The herb is so potent that it is sometimes given in an injectable form in hospital resuscitation rooms to combat the life-threatening, liver-obliterating effects of poisonous mushrooms.  In addition, because excessive alcohol depletes glutathione, milk thistle can aid in protecting the livers of alcoholics or those recovering from alcohol abuse.

 Additional benefits.

In cancer patients, milk thistle limits the potential for drug-induced damage to the liver after chemotherapy, and it speeds recovery by hastening the removal of toxic substances that can accumulate in the body.  The herb also reduces the inflammation and may slow the skin-cell proliferation associated with psoriasis.  It may be useful for endometriosis (the most common cause of infertility in women) because it helps the liver to process the hormone oestrogen, which at high levels can make pain and other symptoms worse.  Finally, milk thistle can be beneficial in preventing or treating gallstones by improving the flow of bile, the cholesterol-laden digestive juice that travels from the liver through the gall bladder and into the intestine, where it helps to digest fats.

How to take it.

Dosage :  The recommended dose for milk thistle is up to 200mg of standardised extract (containing 70% to 80% silymarin) three times a day; lower doses are often very effective.  It is often combined with other herbs and nutrients, such as dandelion, choline, methionine and inositol.  This combination may be labelled ‘liver complex’ or ‘lipotropic factors’.  For proper dosage follow the instructions on the packet.

Guidelines for use : Milk thistle extract seems most effective when taken between meals.  However, if you want to take the herb itself, a tablespoon of ground milk thistle can be sprinkled over breakfast cereal once daily.  Milk thistle’s benefits may be noticeable within a week or two.  The herb appears to be safe, even for pregnant and breastfeeding women.  No interactions with other medications have been noted.

Possible side effects : Virtually no side effects have been attributed to the use of milk thistle which is considered one of the safest herbs on the market.  However in some people it may have a slight laxative effect for a day or two.

Buying guide.

To ensure you are getting the right dose buy products made from standardised extracts that contain 70% to 80% silymarin, milk thistle’s active ingredient. Studies show that preparations containing milk thistle bound to phosphatidylcholine, a constituent of the natural fatty compound lecithin, may be better absorbed than ordinary milk thistle.

When taking milk thistle to alleviate liver damage from excessive alcohol, avoid alcohol based tinctures as they can weaken the resolve to break the addiction.

Recent Findings.

Milk thistle may be a weapon in the fight against skin cancer.  Researchers at Case Western Reserve University in Cleveland, Ohio, found that when the active ingredient, silymarin, was applied to the skin of mice, 75% fewer skin tumours resulted after the mice were exposed to ultra violet radiation.  More studies are needed to see if it has a similar effect in humans.

Final fact.

The components of milk thistle are not soluble in water, so teas made from the seeds usually contain few of the herb’s liver-protecting ingredients.

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Alcohol and Gilbert’s Syndrome

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People with Gilbert’s Syndrome can experience unpleasant reactions when they drink alcohol, although it doesn’t bother some people at all. Here is what happens in the body when you drink:

Alcohol is metabolized extremely quickly by the body – absorbed and metabolized before most other nutrients. About 20% is absorbed directly across the walls of an empty stomach and can reach the brain within one minute.

Once alcohol reaches the stomach, it begins to break down with the alcohol dehydrogenase enzyme. This process reduces the amount of alcohol entering the blood by approximately 20%. (Women produce less of this enzyme, which may help explain why women become more intoxicated than men).

About 10% of the alcohol is expelled in the breath and urine.

Alcohol is rapidly absorbed in the upper portion of the small intestine. The alcohol-laden blood then travels to the liver via the veins and capillaries of the digestive tract, which affects nearly every liver cell. The liver cells are the only cells in our body that can produce enough of the enzyme alcohol dehydrogenase to oxidize alcohol at an appreciable rate.

Though alcohol affects every organ of the body, it’s most dramatic impact is upon the liver. The liver cells normally prefer fatty acids as fuel, and package excess fatty acids as triglycerides, which they then route to other tissues of the body. However, when alcohol is present, the liver cells are forced to first metabolize the alcohol, letting the fatty acids accumulate, sometimes in huge amounts. Alcohol metabolism permanently changes liver cell structure, impairing the liver’s ability to metabolize fats. This is why heavy drinkers develop fatty livers.

The liver can deal with about ½ ounce of ethanol per hour (about one drink, depending on a person’s body size, food intake, etc.). If more alcohol arrives in the liver than the enzymes can handle, the excess alcohol travels to all parts of the body, circulating until the liver enzymes are finally able to process it.

If you are looking after your liver, then it pays to not drink alcohol!

For people with Gilbert’s Syndrome alcohol will likely raise bilirubin levels, and can result in a hangover that’s pretty quick to appear and may last for days.

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Diagnosing Gilbert’s Syndrome

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People with Gilbert’s Syndrome are often diagnosed after a blood test shows a high level of bilirubin in their blood. You may have gone to the Dr with an unrelated problem, or have presented with a number of symptoms such as feeling tired all the time, feeling sick, jaundice (yellow skin or eyes), abdominal pain, IBS, lack of concentration, and generally feeling unwell. At least 30% of people with Gilbert’s Syndrome may have no symptoms at all.

The Dr will first rule out other liver problems, usually through liver function tests on your blood which will show if the liver is damaged as well as checking the level of bilirubin, and provided you have no other easily identifiable problem you may be diagnosed with Gilbert’s Syndrome.

Sometimes tests are conducted before and after a 48 hour fast as this seems to really raise the bilirubin levels in people with Gilbert’s Syndrome. Bilirubin levels in people with Gilbert’s Syndrome can change over time, and so may be missed if they happen not to be raised at the time of the blood test. Bilirubin is measured in millimoles per litre (umol/L). Total serum bilirubin higher than 17 umol/L is outside the normal range.  The bilirubin typically fluctuates in the range of 20 – 40 mmol/L although normal values may occur, and results as high as 80 mmol/L may be seen in patients who have not consumed food for several days. Gilbert’s Syndrome is the most common cause of raised bilirubin levels, however there are rare and more serious conditions such as Criglar-Najjar Syndrome which is inherited from the same gene.

Very rarely a liver biopsy may be performed to rule out other liver conditions, and you may also be offered genetic testing.

Unfortunately, after diagnosis you are likely to be offered little help to deal with your symptoms. However, if you are experiencing nausea, IBS, or other problems you may be prescribed medication that can help.  For other symptoms, well, we’re here to help and hopefully some of the information on this website will help you live better with Gilbert’s Syndrome.

 

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Detoxification – what is it?

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Detoxification – what is it?

OK, this is quite technical, but quite handy to know as background to how your liver works:

The liver is one of the most important organs in the body when it comes to detoxifying or getting rid of foreign substances or toxins. The liver neutralizes a wide range of toxic chemicals, both those produced by your own body and those from the environment.

One of the liver’s primary functions is filtering the blood. Almost 2 quarts of blood pass through the liver every minute for detoxification. Filtration of toxins is absolutely critical as the blood from the intestines contains high levels of bacteria, and various other toxic substances. When working properly, the liver clears 99% of the bacteria and other toxins during the first pass.

Bile Excretion

The liver’s second detoxification process involves the synthesis and secretion of bile. Each day the liver manufactures approximately 1 quart of bile, which serves as a carrier in which many toxic substances are dumped into the intestines. In the intestines, the bile and its toxic load are absorbed by fibre and excreted. However, a diet low in fibre results in inadequate binding and reabsorption of the toxins.

Phase I and Phase II Detoxification

The liver’s third role in detoxification involves a two-step process, Phase 1 and Phase 2. If the phases are out of balance, as in Gilbert’s Syndrome where Phase 2 is impaired, then you are more sensitive to toxins.  These toxins not only include drugs, pesticides, and toxins from the gut, but also normal body chemicals such as hormones and inflammatory chemicals (e.g. histamine) which become toxic if allowed to build up.

Phase I enzymes directly neutralize some chemicals, but most are converted to intermediate forms that are then processed by phase II enzymes. These intermediate forms are much more chemically active and therefore more toxic.

Phase II detoxification typically involves ‘conjugation’. Conjugation is where various enzymes in the liver attach small chemicals to the toxin. This conjugation (or binding together) reaction either neutralizes the toxin or makes the toxin more easily excreted through the urine or bile. Phase II enzymes act on some toxins directly, while others must first be activated by the phase I enzymes. There are essentially six phase II detoxification pathways:

· Glutathione conjugation, Amino acid conjugation, Methylation, Sulfation, Acetylation and , Glucuronidation – this last one is impaired in GS sufferers.

Glucuronidation

Glucuronidation, the combining of glucuronic acid with toxins, requires the enzyme UDP-glucuronyl transferase (UDPGT). Many of the commonly prescribed drugs are detoxified through this pathway. It also helps to detoxify aspirin, menthol, vanillin (synthetic vanilla), food additives such as benzoates, and some hormones. Glucuronidation appears to work well, except for those with Gilbert’s syndrome.

The activity of UDPGT is increased by foods rich in the monoterpene limonene (citris peel, dill weed oil, and caraway oil). Methionine, administered as SAM, has been shown to be quite beneficial in treating Gilbert’s syndrome.

Nutrients needed by phase II detoxification enzymes

Glutathione conjugation: Glutathione, vitamin B6

Amino acid conjugation: Glycine

Methylation: S-adenosyl-methionine

Sulfation: Cysteine, methionine, molybdenum

Acetylation: Acetyl-CoA

Glucuronidation: Glucuronic acid

phase II detoxification enzymes can be encouraged by :

Glutathione conjugation: Brassica family foods (cabbage, broccoli, Brussels sprouts); limonene-containing foods (citrus peel, dill weed oil, caraway oil)

Amino acid conjugation: Glycine

Methylation: Lipotropic nutrients (choline, methionine, betaine, folic acid, vitamin B12)

Sulfation: Cysteine, methionine, taurine

Acetylation: None found

Glucuronidation: Fish oils, cigarette smoking, birth control pills, Phenobarbital, limonene-containing foods

phase II detoxification enzymes can be blocked or slowed down by:

Glutathione conjugation: Selenium deficiency, vitamin B2 deficiency, glutathione deficiency, zinc deficiency

Amino acid conjugation: Low protein diet

Methylation: Folic acid or vitamin B12 deficiency

Sulfation: Non-steroidal anti-inflammatory drugs (e.g. aspirin), tartrazine (yellow food dye), molybdenum deficiency

Acetylation: Vitamin B2, B5, or C deficiency

Glucuronidation: Aspirin, probenecid

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Gilbert’s Syndrome and medication processing

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http://www.sydpath.stvincents.com.au/tests/Gilberts.htm

Recently evidence suggests that people with Gilbert’s syndrome may show increased toxicity compared to unaffected individuals following use of medications which are metabolised by glucuronidation in the liver. This has been reported with some anti-cancer agents and also with paracetamol, where they may be more prone to toxicity after paracetamol overdose.

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The Liver Fortifying Diet

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The liver fortifying diet:

Cut down on the alcohol, salt, caffeine, tobacco, medication, sugar, and fat and stock up on these goodies.  Your liver will love you.

Essential Vitamins and Minerals

Vitamins C and E and minerals zinc and selenium are ‘antioxidants’ shown to aid liver healing. Sources include carrots, tomatoes, peppers, watercress, citrus fruits, berries, wholegrains seeds and oils.

B vitamins and choline are found in egg yolks, liver, legumes and brewer’s yeast and can help liver function.  Make sure your diet contains plenty of green leafy veg rich in folic acid, wholegrains and shellfish rich in vitamin B6, and vitamin B12 foods such as fortified cereals, seafood and seaweed.

 Cruciferous Veg.

Members of the cabbage family have been shown to activate the liver’s cytochrome P450 detoxification process and glutathione conjugation.  In plain English – a process that converts fat-soluble toxins into water-soluble ones, more easy for your body to get rid of.

broccoli cauliflower cabbage
food good for Gilbert's Syndrome

Try include broccoli, cauliflower, kale, mustard greens, radish, brussel sprouts and cabbage in your diet.

Sulphur rich foods.

Garlic, onions, eggs and legumes are rich in sulphur.  They can enhance the sulphuration detoxification process performed by the liver.

Detoxing superfoods.

You should add red fruits, berries, beetroot, and grapes to your diet, as these all help the liver to detoxify and are high in toxin fighting anthrocyanidines.  Papayas and pineapple contain useful enzymes to improve digestion and lemons have a strong cleansing effect.

Helpful Herbs.

Milk thistle, dandelion, turmeric and liquorice have all been shown to aid liver function.  Ginger is also an excellent cleanser.

Good Protein.

The liver needs protein to repair itself, and a diet high in protein gives some people with Gilbert’s Syndrome more energy.  Choose healthy alternatives to red meat such as fish, nuts, pulses and seeds as they are easier to break down and place less of a burden on your liver.

Water.

Once your liver has removed the toxins from your body, you must flush them out of your body.  The only way to do this is to drink lots of water.  Three pints or eight glasses a day minimum!  Although you may find this no problem as some sufferers have expressed how thirsty they seem these days.

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itchy skin

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Do you find a side of effect of your GS is itchy skin?  A lot of us experience it.  One suggestion why this might happen is that your skin, as the bodies 2nd largest detoxification organ after your liver, is trying to help your ailing liver in the detox process.  Here’s a couple of tips that might help – 1) Skin brushing before your morning shower or bath helps to stimulate circulation and encourage detoxification.  Brush towards your heart using firm strokes. 2) If you’ve over indulged and your liver is struggling, swapping your morning-after coffee with a cup of nettle or dandelion tea will replace lost minerals and support your liver’s detoxification process.

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