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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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Itching and Gilbert’s Syndrome

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Many people who have Gilbert’s Syndrome experience itching, which doesn’t seem to be related to any obvious cause and has no visible rash.  I myself have been through the obvious checklist many times: washing powder; cosmetics; food; perfume, but nothing had ever changed as, knowing I itch at the drop of a hat, I’m very careful regarding anything I could be allergic to.

BUT…what if it isn’t any kind of allergy?

The idea never occurred to me  until Adina let me know that it was a query that had come up several times with Gilbert’s Syndrome sufferers.  I have had a look at the information available to the general public and here are some of the interesting facts I found on the subject:-

www.nhsdirect.nhs.uk states that “general itching may be a symptom of many conditions, including…some condition affecting your liver…”  The conditions mentioned include more serious liver conditions than GS in terms of prognosis but this doesn’t rule it out as is it not stated that itching is not a GS syptom.

www.netdoctor.co.uk says of primary biliary cirrhosis that the symptoms are identical to any other chronic liver problem – itching, aches and low energy.  Chronic means long term, Gilbert’s Syndrome is a chronic liver problem, so again, this is indicative that the itching we experience is a symptom of our GS.

I also found some information on the British Liver Trust website (www.britishlivertrust.org.uk) that may explain WHY itching occurs in GS, through an explanation of a different liver condition:-

Itching is stated as a symptom of cholestasis, which is a reduction in the flow of bile from the liver.  This causes bile salts to build up in the blood, be deposited in the skin and cause itching.  Bilirubin increases are suggestive of problems with the bile duct.  Gilbert’s Syndrome is diagnosed due to a long term increase in bilirubin, also classified as ‘bile level’ in blood tests of liver function.

In Gilbert’s Syndrome bilirubin is raised due to lack of an enzyme rather than a blockage of the bile duct.  It was not clear to me from the information I had found so far if an increase in bilirubin goes hand in hand with an increase in bile salts or whether the two are mutually exclusive.  So I read further…

I found quite a lot of work which links bilirubin and bile salts, for example www.revision-notes.co.uk/revision/859.html , in describing the process of bile secretion, states of bile “It is an alkaline, mucous fluid containing bile pigments, biliverdine and bilirubin.  Bile also contains bile salts…”

However, I have not been able to find anything that specifically states that bile salt levels are raised in Gilbert’s Syndrome or whether bilirubin can be increased without bile salts being raised.  It is always stated that of all liver function tests only bilirubin is raised in GS which suggests levels of bile salts are normal, although I do not know if this is tested separately.  If this is the case it is possible that bile salts may fluctuate, even if within normal limits at testing, causing itching on occasion but not constantly.  This is pure speculation but I hope gives us something to think about and ask our GPs next time we have a consultation.

By contributor Nicola Southworth

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The menopause as a trigger of Gilbert’s Syndrome symptoms

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One of the major roles of the liver is to process hormones.  It is therefore not irrational to suppose that the menopause may have some effect on a woman’s experience of Gilbert’s Syndrome (and vice versa) due to the enormous hormonal changes and fluctuations that cause it.

During the menopause the ovaries are less able than before to respond to the pituitary hormones follicle stimulating hormone (FSH) and luteinising hormone (LH), and so less oestrogen is produced.  Due to the reduction of oestrogen production some androgens that are still produced by the adrenal glands, such as testosterone, are not overridden as they were before the onset of the menopause.

This means there is a major shift in the balance of hormones in the body, with an increase of FSH, LH and androgens for the liver to process.

Scouring the recently published scientific research I could not find any article that had investigated the effects of these changes on people with liver conditions.  Common sense suggests that these changes would be an immense shock to the liver (we only have to look at all the other effects on the body to understand that this is a huge physical change).  As the liver metabolises hormones and deactivates them when they are no longer useful, it has an increased workload with the excess FSH, LH and androgens.  It seems highly possible that this extra strain on the liver of someone with Gilbert’s Syndrome would bring to the fore Gilbert’s Syndrome symptoms that had not previously been recognised when the liver was used to the hormonal balance of the body.

Many symptoms of the menopause and of Gilbert’s Syndrome are very similar and so these symptoms may be enhanced in someone with Gilbert’s Syndrome.  For example, the insomnia or disrupted sleep caused by other menopause symptoms, such as hot flushes, can lead to fatigue and generalised aches and pains, common symptoms of Gilbert’s Syndrome.  Other symptoms common to both include dizziness and difficulty with cognitive tasks, such as concentration and memory.

Finally, a word about medication.  The most commonly used treatment to ease the effects of the menopause is HRT.  As yet, we are not fully aware of the exact effects many medications have in relation to GS.  We know some medications are processed differently by GS sufferers and so anyone taking any medication who has GS should be aware of this.  There is evidence that HRT can affect bile composition (http://hcd2.bupa.co.uk), which may have implications for GS sufferers.  It may, therefore, be worth being aware of these scant facts when consulting the GP, in order for them to give the best possible advice for the individual.

Unfortunately, as yet, there are no answers to the dual problem of the menopause with Gilbert’s Syndrome, apart from the advice to everyone with Gilbert’s Syndrome: to do everything in our power to reduce the workload of our liver

(originally written by contributor Nicola Southworth)

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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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Welcome to the all new Action on Gilbert’s Syndrome web

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Welcome to the all new Action on Gilbert’s Syndrome website. We’re currently in development to bring you the latest up to date info on Gilbert’s Syndrome in an easy to access site. If you want updates on our progress just sign up on the right! =>

One in 20 people may have Gilbert’s Syndrome (or possibly more), but only one in three of those will be aware of it, and less than one in three will have any symptoms at all. Most people who have it are men. Sometimes called Gilbert’s Disease, it is not in fact a disease.

Most Doctors use standard reference information that tells them to tell you that Gilbert’s Syndrome is harmless. However, information from scientific studies illustrates that you may experience a number of symptoms, including the most common one of jaundice, and that you need to be aware of certain chemicals, including prescription medication, that you are less able to cope with.

This website offers those with Gilbert’s Syndrome, and their family and friends, as well as the medical profession, further information from published scientific research and shared information from hundreds and thousands of individuals who have Gilbert’s Syndrome.

I hope it helps us all live better with Gilbert’s Syndrome.

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