Gilbert's Syndrome | The Detoxification System | Understanding the Mutations | GS Symptoms | Things That Help & Things To Avoid
Connections To: Allergies | Chronic Fatigue Syndrome | Candida | Soy | Hypothyroidism

Gilbert's Syndrome

Contents: Introduction | The Basics | Known Effects | Original Onset & Symptom Triggers | Connections To Other Problems | Great Sites


This site is dedicated to the understanding of Gilbert's Syndrome and its many symptoms and related problems. It's dedicated to answers, and I invite people with GIlbert's Syndrome (GS), doctors, researchers, friends, family, and any other interested people to take part in understanding this genetic condition and everything related to it. There is still a lot to discover, and will take a combination of science and personal experience to put the picture together.

The Gilbert's Syndrome Story

If you're like many people diagnosed with Gilbert's Syndrome, you've been on a long journey to find out what's wrong with you, visiting doctor after doctor and coming up with nothing. And then one day, a doctor tells you that you have Gilbert's Syndrome but that it's not the cause of your problems because their desk reference says that there are no symptoms. At that point the doctors usually tell you that all your symptoms are probably due to stress or depression. Worse still, some will claim you're a hypochondriac or making it all up. Rather than listening to your symptoms and looking for an explanation, you are sent on our way without help.

There are several scientific studies examining the many and varied effects of Gilbert's Syndrome, but apparently they havent found their way into the desk references yet. The fact is that there is a striking degree of similarity in the symptoms suffered by those with Gilbert's Syndrome, and these symptoms can be incredibly disruptive to one's life. Luckily, it is not life threatening. But this may also be the reason is doesnt get the attention it deserves.


From an exhaustive study of the symptoms reported by 283 people with Gilbert's Syndrome on the Gilbert's Web forums over the past 5 years, here are the symptoms of Gilbert's Syndrome.

Frequently Reported: fatigue, tiredness, brain fog, headaches, poor memory, dizziness, depression, irritability, anxiety, nausea, loss of appetite, irritable bowel syndrome (IBS), stomach pain & cramping, liver/gallbladder pain, abdominal pain, tremors, itchiness, jaundice

Commonly Reported: insomnia, difficulty concentrating, panic attacks, hypoglycemic reaction to foods, intolerance to carbs, food intolerances, alcohol intolerance, loose stools / diarrhea, abdominal bloating or swelling, breathlessness or labored breathing, heart palpitations, aching muscles / body ache, joint pain, numbness & tingling, weakness, chemical sensitivity, weight loss, lump in the throat, feeling constantly sick

Sometimes Reported: difficulty finding the right words, feeling drunk, vomiting, intolerance to fatty foods, strong hangovers, acid reflux, excessive thirst, chest pain, muscle twitches, cold hands and feet, environmental allergies, swollen lymph nodes, toxic feeling, bitter or metallic taste in the mouth, eye pain

Occasionally Reported: waking panic attack, mood swings, feeling antisocial, intolerance to drugs, constipation, pale stools, indigestion, back pain, dry skin, feeling cold, low body temperature, pale skin, low weight, night sweats, excessive sweating, poor immune system, sore or dry throat, light sensitivity, bloodshot eyes

Many of these I have connected either directly to Gilbert's Syndrome or via effects caused by GS. As to the rest, I'm investigating the following possibilities:

* Gilbert's Syndrome directly causes these symptoms
* Gilbert's Syndrome directly causes or increases the likelihood of related problems which cause these symptoms
* These symptoms are caused by other problems entirely, and GS is incidental (this is appearing less and less likely)

Gilbert's Syndrome - The Basics


Gilbert's Syndrome was first described in 1901 as a syndrome of chronic, benign, intermittent jaundice in the absence of other liver diseases. They described psychological symptoms that included the historical equivalent of chronic fatigue syndrome.'s%20Syndrome.htm

In 1901, Gilbert and Lereboullet described a syndrome of chronic, benign, intermittent jaundice, characterized by mild hyperbilirubinemia in the absence of bilirubinuria or symptoms and signs of liver disease.

Gilbert et al originally described a clinical syndrome associated with hyperbilirubinaemia. They described psychological symptoms that included neurasthenia, the historical equivalent of chronic fatigue syndrome.

What It Is

The body has a two-phase detoxification system. Depending on the toxin, the first phase can either detoxify it entirely or prepare it for the second phase. In the second phase there are several major systems which act on these toxins. The one affected by Gilbert's Syndrome is the glucuronidation system, which "conjugates" the toxins so they can be removed from the body. Enzymes in the glucuronidation system are called uridine diphosphate glucuronyl transferase, or UGT for short. UGT1A1, for example, refers to a specific enzyme in this family.

Gilbert's syndrome is due to a genetic mutation that causes only 30% of the enzyme UGT1A1 to be produced. This is the only enzyme that detoxifies bilirubin, a toxic product of the natural breakdown of red blood cells. This enzymatic shortage leads to an excess of bilirubin (and other toxins) in the blood serum. Most people with Gilbert's Syndrome also have linked mutations in two other enzymes - UGT1A6 and UGT1A7, causing similar enzyme shortages which leads to their related toxins circulating in the body for longer periods as well. The things acted upon by these enzymes include many carcinogens, drugs, hormones, and various other toxins.

You may want to visit the section on the body's detoxification system before continuing, as it will explain a lot about how it all works.

PERSONAL: Gilberts Web Forums

Gilbert's Syndrome
By Marina Eckel

Gilbert’s syndrome has been long recognized as the inability to detoxify bilirubin, a breakdown product of hemoglobin. This inability causes the pigment to be recirculated through the body and results in a slight yellowish tinge to the skin, jaundice in the absence of hepatitis. This condition is hereditary. Five to seven percent of the general population is diagnosed with this condition, which has been determined to be “benign” by the allopathic community. High levels of bilirubin in the blood as well as yellowish skin are diagnostic markers. It is more often diagnosed in men, but this may be due to the fact that more young men than women are undergoing complete physicals as part of the recruitment process into the military. New research is showing that this “benign” condition is actually a deeper condition which requires recognition and slight control of lifestyle in order to be optimally lived with. Many individuals report symptoms of chronic fatigue and headaches associated with GS. These symptoms are most likely the effect of a weary liver, overburdened with toxins which are difficult to eliminate.

Gilbert’s Syndrome is a condition which is quickly gaining recognition. Gilbert’s Syndrome (GS) is a genetic and therefore inherited condition which is characterized by a defect in the Phase II detoxification enzyme UDP-Glucuronyl transferase (UDPGT) which is responsible for the glucuronidation detoxification pathway in the liver. People who have this condition are inefficient in detoxifying and conjugating both endogenous and exogenous toxins which require the glucuronidation pathway for elimination from the body. One endogenous component which requires this pathway is bilirubin which has been discussed above. New research is showing that glucuronidation is an important detoxification pathway for many other substances and that individuals who have this disorder are more susceptible to toxic reactions to xenobiotics and drugs. {Pizzorno, 156}.

BACKGROUND. People with Gilbert's syndrome have mild, chronic unconjugated hyperbilirubinemia in the absence of liver disease or overt hemolysis. Hepatic glucuronidating activity, essential for efficient biliary excretion of bilirubin, is reduced to about 30 percent of normal.

Gilbert’s syndrome is caused by decreased hepatic levels of the enzyme glucuronosyltransferase. As this enzyme is responsible for the glucuronidation (conjugation) of bilirubin in the liver, reduced activity of this enzyme leads to an accumulation of unconjugated bilirubin in the circulation. The genetic defect has been identified as the presence of two additional nucleotides in the promoter region of the gene leading to reduced gene expression and therefore reduced enzyme activity. In affected individuals the enzyme is usually functioning at about 25% of normal levels. Of interest the syndrome may be passed to recipients of liver transplantation if the donor was affected.

Unconjugated hyperbilirubinemia in Gilbert syndrome has long been recognized as due to underactivity of the conjugating enzyme system bilirubin-uridine diphosphate glucuronyl transferase (bilirubin-UGT). Bilirubin-UGT is responsible for conjugating bilirubin into bilirubin monoglucuronides and diglucuronides and is located primarily in the endoplasmic reticulum of hepatocytes. Bilirubin-UGT is one of several UGT enzyme isoforms responsible for the conjugation of a wide array of substrates that include carcinogens, drugs, hormones, and neurotransmitters.

Genetic lesions of the bilirubin conjugating enzyme uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1) cause both Gilbert's and the much rarer Crigler-najjar syndromes. In Gilbert's syndrome the mutation has recently been identified as affecting the promoter gene of the enzyme, while the structural gene coding for the protein itself is normal. Hepatic glucuronidation is reduced to around 30% of normal.

A case report of Gilbert Syndrome.
Virtually all patients have decreased level of UDP-Glucuronosyltransferase, but there also is evidence for a defect in hepatic uptake of bilirubin as well.
The hyperbilirubinemia is mild and by definition < 6 mg/dl. However, most patients exhibit levels of 3 mg/dl. Considerable daily and seasonal variations are observed and bilirubin level occasionally may be normal in as many as one-third of patients.
Gilbert syndrome is a benign condition with no associated morbidity or mortality affecting all races occurring predominantly in men with a male to female ratio ranging from 2:1-7:1. It usually is  diagnosed around puberty, possibly due to inhibition of bilirubin glucuronidation by endogenous steroid hormones. In older subjects, the diagnosis is usually made when unconjugated hyperbilirubinemia is noted on routine blood tests or unmasked by an intercurrent illness or stress.

Note: Is this poorly worded, or is it saying that the entire Glucuronidation system is effected?



I have seen a wide range of frequency statistics for GS, from 2% to 23%. The most commonly reported range, however, is 5%-10%. In populations of Africa and the Indian subcontinent, the frequency is 10-25%, and in Southeast Asia and the Pacific Islands the frequency is 0-5%.

SCIENCE: National Library of Medicine

On the basis of serum bilirubin levels, 3 to 10 percent of the general population are estimated to have Gilbert's syndrome.

Gilbert's syndrome occurs in 5%-7% of the human population


The frequency of (TA)7 homozygotes has been reported to be about 0.5–23% in various populations.

Gilbert's syndrome often remains undiagnosed and occurs in up to 19% of individuals.

Homozygosity for the promoter variant is frequently encountered in European and African populations with a prevalence of 11% to 19%.

Homozygosity for the (TA)(7) allele occurs in 10-25% of the populations of Africa and the Indian subcontinent, with a variable frequency in Europe. It occurs at a much lower frequency in Southeast Asia, Melanesia, and the Pacific Islands, ranging from 0 to 5%.


Age of Diagnosis & Onset

It appears that the majority of people begin experiencing symptoms of GS in their 20s-30s, more commonly at the age of 25-30. For more on the original onset of symptoms, see the section below, "Original Onset and Symptom Triggers".

Gilbert syndrome is usually diagnosed around puberty, possibly because of the inhibition of bilirubin glucuronidation by endogenous steroid hormones. In older persons, the diagnosis is usually made when unconjugated hyperbilirubinemia is noted on routine blood test results or unmasked by an intercurrent illness or stress.

Note: Endogenous steroids further inhibit bilirubin glucuronidation (makes it worse).


Symptoms (major section)

This section investigates the symptoms associated with Gilbert's Syndrome. There is specific range of symptoms that are reported again and again with Gilbert's Syndrome, and this section gives an explanation of them, as well as hundreds of personal accounts. See the full text on the Symptoms page.

Things That Help, Things To Avoid (major section)

Without much help from the medical community, it's fallen to those with Gilbert's Syndrome to figure out what helps with the symptoms and what makes them worse. See the full text on the Things That Help, Things To Avoid page.


Testing for Gilbert's Syndrome

Elevated bilirubin levels are not enough to diagnose GS. The two primary reasons they can be elevated are from liver problems or blood problems (as in anemia, where too much bilirubin is produced). There are genetic tests for Gilbert's Syndrome, but it might be hard to get covered by insurance.

The best route is to be tested for liver problems, blood problems, and bilirubin levels. The liver test is called a 'liver function test'. For the bilirubin test, have your total bilirubin, conjugated bilirubin, and unconjugated bilirubin levels tested. When total bilirubin is elevated, unconjugated bilirubin is making up a large majority of your total bilirubin count, and no other liver or blood problems are apparent, Gilbert's Syndrome is properly diagnosed.

This made it necessary to search for ancillary factors that might modify the serum bilirubin concentration in persons homozygous for the promoter defect. These factors could include hepatic transport abnormalities, occult hemolysis, and stress-related induction of heme oxygenase.

Bilirubin Reference Range

In the US mg/dl is used as the units for bilirubin measurement, while most of the rest of the world uses μmol/L. Different labs have different reference ranges, so I've listed those I could find here:

PERSONAL: Gilberts Web Forums

mg/dl measurements: (mg/100ml)
Total: 0.1 to 1.2, 0.2 to 1.5, 0.2 to 1.3, 0.3 to 1.4
Indirect/Unconjugated: 0 to 1.3, 0.1 to 0.7, 0 to 0.7
Direct/Conjugated: 0 to 0.3, 0 to 0.5, 0.1 to 0.4
Used in US
μmol/l measurements:
Total: 1 to 18, 0.2 to 22, 2 to 20
Indirect/Unconjugated: .2 to 12
Direct/Conjugated: 0 to 8
Used in New Zealand, UK

Note: These are also taken from my own test result pages and medical web sites. The numbers at Wikipedia were off the last time I checked, with numbers too low un umol/l and too high in mg/dl.


The Body's Detoxification System (major section)

It is helpful at this point to understand the body's detoxification system. This page gives a detailed picture of the different enzyme systems used in detoxification of any toxins the body comes into contact with, either internally or externally. Understanding this will help make clear what follows.



This goes into more detail about the genetic mutation responsible for Gilbert's Syndrome. Genetic mutations are given a asterisk notation, and the mutation causing Gilbert's Syndrome is called UGT1A1*28. The mutation is not in the structure of the enzyme, which is fine, but in the amount of it that is produced. The area responsible for this is called the promoter region. In Caucasian and African populations, this is the most common cause of Gilbert's Syndrome, while in Japanese populations, a mutation known as G71R alters the effectiveness of the UGT1A1 enzyme with nearly identical results.

A breakthrough in understanding the genetic basis of Gilbert syndrome was achieved in 1995, when abnormalities in the TATAA region of the promoter were identified. The addition of 2 extra bases (TA) to the TATAA region interferes with binding of the transcription factor IID and results in reduced expression of bilirubin-UGT1 (30% of normal).

SCIENCE: National Library of Medicine

The Genetic Basis of the Reduced Expression of Bilirubin UDP-Glucuronosyltransferase 1 in Gilbert's Syndrome

Glucuronidation & Androgenic Steroids (my heading)
Among the normal subjects, only men who were homozygous for the longer TATAA element had significant elevations in serum bilirubin levels, reflecting a greater bilirubin load in men per kilogram of body weight or the inhibition of enzymatic glucuronidation by androgenic steroids (or both). This finding is consistent with the high male-to-female ratio among patients with diagnosed Gilbert's syndrome.
Enzyme is Fine, Amount is Low (my heading)
The coding region of the gene for the enzyme was normal in the 10 patients with Gilbert's syndrome.
Our functional studies showed that the presence of the longer TATAA element in the upstream regulatory region of the gene reduces the expression of a reporter gene in a human hepatoma cell line. Together, these results suggest that the decreased bilirubin glucuronidating activity in Gilbert's syndrome results from reduced expression of the bilirubin glucuronidating enzyme.

The presence of this longer TATAA element in the promoter region of the gene for bilirubin UDP-glucuronosyltransferase 1 resulted in reduced expression of a reporter gene, encoding firefly luciferase, in a human hepatoma cell line
Gilbert's Syndrome Requires Both Genes To Have the Defect (my heading)
These patients were homozygous for two extra bases (TA) in the TATAA element of the 5' promoter region of the gene (A(TA)7TAA rather than the normal A(TA)6TAA). The presence of the longer TATAA element resulted in the reduced expression of a reporter gene, encoding firefly luciferase, in a human hepatoma cell line. The frequency of the abnormal allele was 40 percent among the normal subjects. The 3 men in the control group who were homozygous for the longer TATAA element had significantly higher serum bilirubin levels than the other 52 normal subjects (P = 0.009).

But There’s More To It (my heading)
All 10 patients with Gilbert's syndrome were homozygous for the longer TATAA element, suggesting that reduced expression of bilirubin UDP-glucuronosyltransferase 1 is essential for the syndrome. However, a mild reduction in the enzyme is not always sufficient for the full manifestation of the phenotype. Our results indicate that as much as 16 percent of the population should be homozygous for the long TATAA element, whereas only 3 to 10 percent of the general population have clinically diagnosed Gilbert's syndrome.
UGTA1A Expression is 30% of Normal (my heading)
Hepatic glucuronidating activity, which is essential for efficient biliary excretion of bilirubin, is approximately 30 percent of normal in patients with Gilbert's syndrome. The reduced glucuronidation results in an increased proportion of bilirubin monoglucuronide in bile. In human liver, bilirubin glucuronidation is mediated by one specific isoform of microsomal bilirubin, UDP-glucuronosyltransferase (bilirubin/uridine diphosphoglucuronate-glucuronosyltransferase). Of the two isoforms reported, only bilirubin UDP-glucuronosyltransferase 1 contributes substantially to bilirubin glucuronidation.

 Note: I wrote to one of the scientists who conducted this experiment to clarify whether all glucuronidating activity was running at 30% or just that of UGT1A1, and he replied that it was just UGT1A1 and its substrates, including some estrogens, several drugs and some carboxylic acid xenobiotics. He continued, "In theory, glucuronidation mediated by other UGT isoforms should not be affected (although this has not been verified directly)."

Other Causes for High Bilirubin Counts (my heading)
Although hemolysis is not part of the syndrome, many patients who consult physicians may have a high bilirubin load because of a slightly reduced erythrocyte life span. Fasting may also increase the bilirubin load, and the resulting hyperbilirubinemia may be exaggerated in patients with Gilbert's syndrome because of the reduced expression of the glucuronidating enzyme.

SCIENCE: National Library of Medicine

Official Symbol: UGT1A1
Official Name: UDP glucuronosyltransferase 1 family
Gene aliases: GNT1; UGT1; UDPGT; UGT1A; UGT1*1; HUG-BR1
Summary: This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The preferred substrate of this enzyme is bilirubin, although it also has moderate activity with simple phenols, flavones, and C18 steroids. Mutations in this gene result in Crigler-Najjar syndromes types I and II and in Gilbert syndrome.

Most patients with Gilbert's syndrome may have abnormalities in glucuronidation of aspirin or coumarin- and dopamine-derivatives, due to this combination of UGT1A1*28 and UGT1A6*2 genotypes.

DP glucuronosyltransferase 1 family, polypeptide A1

Alternate Names: UDP glucuronosyltransferase 1A1; UDP glycosyltransferase 1 family, polypeptide A1; UGT1A; bilirubin UDP-glucuronosyltransferase 1-1; bilirubin UDP-glucuronosyltransferase isozyme 1

Alternate Symbols: GNT1; HUG-BR1; UDPGT; UGT1; UGT1*1; UGT1A; UGT1A5

SCIENCE: National Library of Medicine (PDF)

Heterozygous G71R-mutation causing Gilbert's syndrome in one of 103 random persons of German descent

In the European and African population, most frequently the promoter of the gene is affected by a dinucleotide polymorphism in the TATAA box promoter, which was recently named UGT1A1*28 [1,3]. This insertion has been shown only in 3% of the Asian population. A second common heterozygous mutation in the coding exon 1 of the (UGT-1A1) gene (G71R) is the main mutation in Asia [4]. So far the (G71R) mutation has only been shown in a young German male suffering from Crigler–Najjar syndrome type II [5].

SCIENCE: The Institute of Biomedical Science

Gilbert's Syndrome

In 1995 the Japanese researchers looked at the DNA recovered from the white blood cells of patients with Gilbert's disease in the search for mutations in the gene (UGT1A1) which codes for UDP-GT production. Mutations in the gene would hopefully explain the observed reduction in activity of the enzyme. The most common mutation in their series of Gilbert's syndrome patients was a missense mutation at nucleotide 211 in exon 1 of UGT1A1. The substitution of the base adenine for guanine changed the codon from GGA to AGA. The enzyme that results from this single base substitution has the amino acid arginine instead of glycine at position 71.

They subsequently demonstrated that the enzyme which results from this mutation (G71R) has 32% and 60% of normal activity for the homozygous and heterozygote states, respectively.

Note: This alternate location for the mutation, if I recall, is more common in Japanese people with GS.


Gilbert's Syndrome Mutations (major section)

This major section goes into details about what the mutations defining Gilbert's Syndrome are. There is one primary mutation which was what caused GS to be discovered in the first place, and two linked mutations that the vast majority of people with GS also have. They are all connected with enzyme deficiencies. This section goes into detail about all the things usually detoxified by these deficient enzymes.



To have Gilbert's Syndrome, one must inherit the mutant gene from both parents. In other words, they must be "homozygous". Those with only one gene have slightly elevated bilirubin levels, but do not have Gilbert's Syndrome.

Every affected person has two copies of the abnormal gene responsible for Gilbert's syndrome. Because over half of the people in the general population have at least one abnormal copy of the gene, inheriting two abnormal copies (one from your mother and the other from your father) is not uncommon. Interestingly, people who have only one copy may have slightly higher levels of unconjugated bilirubin but do not have Gilbert's syndrome.;jsessionid=15i5adt53qjbg?tname=gilbert-s-syndrome&curtab=2222_1&hl=glucuronidation&sbid=lc07a

The gene for Gilbert syndrome has been mapped to chromosome 2. The syndrome is inherited in an autosomal dominant manner. If someone has Gilbert syndrome, the chance of their transmitting the Gilbert gene to each of their children is one-half (50%) and each child who receives the gene has Gilbert syndrome.

SCIENCE: National Library of Medicine

Although the syndrome is inherited, many people do not have a clear family history. An autosomal mode of inheritance has been proposed, and more recently, a recessive pattern of inheritance has been suggested.


Known Effects of Gilbert's Syndrome

Swollen Liver / Liver Hypertrophy

[Ultrasonic examination of the epigastrium in persons with Gilbert's syndrome]

In 29 subjects with Gilbert's syndrome during ultrasonographic examination of the epigastrium in real time a significantly larger anteroposterior dimension of the right liver lobe (by cca 11%] was found. In the other investigated dimensions no significant deviations were found, not even a significantly higher echogeneity of the liver parenchyma. In two instances multiple cholecystolithiasis was detected. Sonography, a non-invasive method with a high yield, is an important link in the examination programme of subjects with Gilbert's syndrome.

Note: Epigastrium = Abdomen. Cholecystolithiasis are gallstones. The right lobe is the larger lobe on one's right side. Anteroposterior means viewed from front to back.

Liver ultrastructure in Gilbert's syndrome.

Electron microscopy of hepatic tissue obtained by percutaneous needle biopsy from nine patients with Gilbert's syndrome has revealed in every case gross hypertrophy of hepatocyte agranular endoplasmic reticulum but no other important abnormality.

Hypertrophy is the increase of the size of an organ. It should be distinguished from hyperplasia which occurs due to cell division; hypertrophy occurs due to an increase in cell size rather than division.

Liver Webs

Pericanalicular microfilaments of hepatocytes in patients with familial non-hemolytic hyperbilirubinemia.

We observed pericanalicular webs (PCW) of liver cells in cases with familial non-hemolytic hyperbilirubinemia using electron microscopy. The area and width of PCW were determined by morphometric methods as a way of quantitating this feature. The mean PCW width was 0.175 +/- 0.003 micron (mean +/- SE) in Dubin-Johnson syndrome and 0.184 +/- 0.005 micron in Rotor's syndrome. In both of these syndromes PCW width was significantly larger than that in Gilbert's syndrome (0.124 +/- 0.003 micron) (p less than 0.01). The mean PCW area was 0.585 +/- 0.017 micron 2 in Dubin-Johnson syndrome and 0.582 +/- 0.030 micron 2 in Rotor's syndrome. Values in these two syndromes were significantly larger than that in Gilbert's syndrome (0.382 +/- 0.014 micron 2) (p less than 0.01). Widths and areas of PCW in these three syndromes were not significantly different between central, intermediate, and peripheral zones of the hepatic lobules. There was a positive correlation between serum direct bilirubin levels and widths or areas of PCW in these syndromes. These results suggested that disturbances of bile flow caused by the dysfunction of pericanalicular microfilaments are partly involved in the pathogenesis of Dubin-Johnson syndrome and Rotor's syndrome.

Increased Toxicity

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.


Jaundice is the most well-known symptom of Gilbert's Syndrome among doctors, and perhaps the first and only symptom mentioned. Jaundice itself is the cause of a feeling of itchiness, and can be associated with dark urine and light stools.

Besides the cosmetic issues of looking yellow and having dark urine and light stools, the symptom that is associated most frequently associated with jaundice or cholestasis is itching, medically known as pruritus. The itching associated with jaundice and cholestasis can sometimes be so severe that it causes patients to scratch their skin “raw,” have trouble sleeping, and, rarely, even to commit suicide.

Increase of Neonatal Jaundice

Gilbert syndrome accelerates development of neonatal jaundice.

Although peak jaundice levels did not differ among groups, newborn infants with the molecular marker for GS have an accelerated increase in neonatal jaundice during the first 2 days of life.

Essential Tremor

[Gilbert's syndrome: a clinicogenetic trial]
In homozygous carriers GS was characterized by a higher baseline level of bilirubin, distinct response to functional tests, frequent combination with essential tremor.

Immune Suppression

The suppressive effect of continuous infusion of bilirubin on the immune response in mice.

Mice (strains Balb/c and A/J) received an intravenous infusion of bilirubin for a 1 d period. The infusion was delivered at various phases of the primary reaction; the degree of the immune response was expressed as the number of antibody-forming cells against sheep erythrocytes. Bilirubin infusion during both the inductive and productive phase of the primary reaction decreased significantly the immune response. We assume that bilirubin influences the differentiation of immunocompetent cells immediately after their contact with the antigen; in addition it acts in the period of the quantitative increase of the number of antibody-producing cells.

Increased Hemolysis (Red Blood Cell Death)

SCIENCE: National Library of Medicine

Study of the etiology and pathogenesis of low grade nonhemolytic unconjugated hyperbilirubinemia (Gilbert's disease).

In 61% of patients a moderately shortened erythrocyte life span has been revealed. However the increased bile pigment production in these cases does not speak against Gilbert's disease. The results of biochemical assays have shown that in n.u.h not only the intrahepatic bilirubin metabolism is disturbed but other functions of the liver cell as well.

Note: Erythocyte = red blood cell.

Note: This could account for the fatigue associated with Gilbert's Syndrome.

SCIENCE: National Library of Medicine

Hemolysis and Bilirubin Conjugation in Association With UDP-Glucuronosyltransferase 1A1 Promoter Polymorphism

Hemolysis may contribute to hyperbilirubinemia in Gilbert's syndrome. The authors examined blood carboxyhemoglobin corrected for inspired CO (COHbc) to index heme catabolism and serum conjugated bilirubin fractions to reflect bilirubin conjugation. Both parameters were related to UDP-glucuronosyltransferase 1A1 (UGT) promoter polymorphism, associated with Gilbert's syndrome, in term male newborns. COHbc was expressed as percentage of total hemoglobin, and total conjugated bilirubin (TCB) value as a percentage of serum total bilirubin (STB), (TCB/STB[%]). A production/conjugation index, COHbc/(TCB/STB[%]), represented bilirubin production divided by conjugation. UGT promoter genotype was designated according to the number of promoter TA insertions in each allele: 6/6, homozygous normal; 6/7, heterozygous; 7/7, homozygous variant. STB and COHbc values were higher in the 7/7 subgroup than the other counterparts (P <.01). The COHbc/(TCB/STB[%]) was higher in the 7/7 than either the 6/6 or 6/7 subsets (1.93 [1.31-2.88] vs. 0.85 [0.51-1.72] and 0.84 [0.53-1.87], respectively; P <.01). In conclusion, 7/7 UGT promoter polymorphism was associated with increased blood COHbc values (unexpected finding) as well as diminished serum total conjugated bilirubin ratios (expected finding). The increased hemolysis may contribute to the pathogenesis of increased STB values seen in Gilbert's syndrome, and exacerbate neonatal hyperbilirubinemia associated with the promoter polymorphism.

(The following is from the entire study via PDF)

Although Gilbert's syndrome is not associated with overt evidence of hemolysis, a shortened red cell life span has been found in some affected individuals.
The COHbc/(TCB/STB[%]) was significantly higher in those with the 7/7 variant promoter (1.93 [1.31-2.88]) than both subgroups with the 6/6 or 6/7 promoters (0.85 [0.51-1.72] and 0.84 [0.53-1.87], respectively; P _ .01)… Within the subgroup of infants homozygous for the variant UGT promoter, COHbc values did not correlate with STB values (r _ 0.06, P _ .8), nor was there any difference in STB values between the subgroups with COHbc values below mean or greater than mean (156 _ 42 _mol/L versus 155 _ 32 _mol/L); implying uniform distribution of hemolysis throughout the subgroup.
What was surprising was the significantly higher mean COHbc value in the 7/7 subgroup, making it apparent that the underlying abnormalities associated with 7/7 UGT promoter polymorphism include both increased hemolysis and diminished bilirubin conjugation.
The mechanism for the increased hemolysis associated with 7/7 UGT promoter polymorphism is currently unknown and will require further study. Although direct bilirubin toxicity to red blood cells in vitro has been described, such toxicity occurred at concentrations of bilirubin far in excess of those encountered in the present study population. Further evidence that plasma bilirubin itself does not cause hemolysis in vivo is that hemolysis is not seen in patients with Crigler-Najjar syndrome. Thus, in the absence of either icterus as an identifying factor or presence of very high STB levels, it is now evident that both increased hemolysis as well as diminished bilirubin conjugation are inherited as genetically determined defects associated with the variant UGT gene promoter.
The principle of COHbc determinations in the assessment of heme catabolism is that equimolar quantities of CO and biliverdin (subsequently bilirubin) are released from heme by the action of the enzyme heme oxygenase. Measurement of COHbc reflects the endogenous CO production, offering accurate assessment of bilirubin production. In the human body, the predominant (85%) endogenous source of CO is from the degradation of heme by heme oxygenase, with only a small proportion originating from non-heme sources; therefore, measurement of blood COHbc reflects primarily the rate of bilirubin formation from hemoglobin.

In Short: Those with Gilbert's Syndrome have increased hemolysis (breaking open of red blood cells) as well as decreased UGT1A1 activity. Subjects have increased blood carboxyhemoglobin levels. The study deduces that the level of carboxyhemoglobin in the blood is due to hemolysis. This hemolysis may contribute to the serum total bilirubin levels, but is not caused by the higher levels of bilirubin in the blood. I wonder if it could also be due to increased carbon monoxide levels from our failure to break it down via the linked mutation in UGT1A7? Actually, I'm not sure what enzyme breaks down CO. The levels of carboxyhemoglobin found in the study (of babies) were around 0.9% for people with GS and 0.7% for the controls. This is a small difference and most likely would never lead to any problems from elevated carboxyhemoglobin.

REFERENCE: Wikipedia - Hemolysis

Hemolysis is the breaking open of red blood cells and the release of hemoglobin into the surrounding fluid (plasma, in vivo).

Carboxyhemoglobin level of 0.4 to 0.7 percent is normally present in the blood of adults. In cigarette smokers, the range is 4 to 20 percent.

Symptoms such as headaches, dizziness and fatigue... can occur with a COHb blood saturation levels of 10-30%. At 30-50% COHb symptoms are nausea, severe headaches, dizziness, and increased pulse and respiration.

In Short: The difference in carboxyhemoglobin (0.9% vs 0.7%) is so slight as to be WELL below the range causing symptoms. So while problems with carbon monoxide are unlikely, the increased red blood cell death probably has an effect of its own.

Gastroparesis - Delayed Gastric Emptying

Delayed gastric emptying in subjects with Gilbert's syndrome

BACKGROUND/AIMS: Recently, it has been proposed that decreased intestinal motility in fasting-induced hyperbilirubinemic rats probably results in an increase in the enterohepatic cycling of unconjugated bilirubin. We investigated the association among gastric emptying, intestinal transit time, and serum unconjugated levels in subjects with Gilbert's syndrome. RESULTS: The gastric emptying in Gilbert's syndrome subjects was 134.1 +/- 38.9 and 90.9 +/- 6.5 min in controls, P < 0.03. It was a tendency to have a shorter intestinal transit time in subjects with Gilbert's syndrome, 138.3 +/- 59.0, than in control subjects, 183.8 +/- 11.3 min. Serum unconjugated bilirubin levels (mg/dL) were 2.6 +/- 1.04 and 0.95 +/- 0.34, P < 0.01. CONCLUSIONS: Gastric emptying is delayed significantly in Gilbert's syndrome, and intestinal transit time differences between Gilbert's syndrome subjects and controls were not significantly different.

Was diagnosed with GS a few months ago. Ironically am doing a PhD in measuring gastric emptying rates and contractility. There is evidence to suggest that people with GS have delayed gastric emptying, ie. the stomach take longer to empty whatever meal has been eaten. This would imply that people with GS feel full early and tend to eat little and often. It also implies that if you do have a large meal, you may suffer from heartburn as the stomach is full for longer.

This would explain a hell of a lot for me. I also find that feelings of fatigue are much worse after eating. This is particularly true for high carb foods.

A study has shown that gastric emptying times are delayed in gilbert sufferes ,maybe thats why we have more burping ,reflux and a feeling of lump in the throat.

In addition to nausea and vomiting, gastroparesis often causes:
• A feeling of fullness after just a few bites (early satiety)
• Abdominal bloating
• Heartburn or gastroesophageal reflux
• Changes in blood sugar levels
• Lack of appetite
• Weight loss and malnutrition

Causes: Other disorders. A number of other medical conditions can cause gastroparesis, including anorexia and bulimia, the connective tissue disease scleroderma, Parkinson's disease and other nervous system illnesses, and metabolic disorders such as hypothyroidism. For reasons that aren't clear, some otherwise healthy people develop gastroparesis after a bout of the flu or other viral illness.

Food in the stomach is ground into tiny pieces by the constant churning that is generated by the contractions of the stomach’s muscles. Once the food has been adequately ground, it slowly is emptied from the stomach into the intestine in a metered fashion. Only food ground into small particles can be emptied from the stomach in a normal fashion, and smaller particles are digested better in the intestine. Moreover, the metering process allows the emptied food to be well-mixed with the digestive juices of the intestine, pancreas, and liver (bile) and to be absorbed well from the intestine.

Symptoms: The primary symptoms of gastroparesis are nausea and vomiting. Other symptoms of gastroparesis include abdominal pain, bloating, early satiety (feeling full quickly when eating), and in severe cases, weight loss due to a reduced intake of food because of the symptoms. Reduced intake of food and restriction of the types of food that are eaten can lead to nutritional deficiencies.

Other, less frequent effects of gastroparesis are the promotion of gastroesophageal reflux disease (GERD) and malnutrition.

Causes: Occasionally, gastroparesis is caused by nervous reflexes, for example, when the pancreas is inflamed (pancreatitis). In such cases, neither the nerves nor the muscles are diseased, but messages are sent through nerves from the pancreas to the stomach which prevents the muscles from working normally. Other causes of gastroparesis include imbalances of minerals in the blood such as potassium, calcium or magnesium, medications (such as narcotic pain-relievers), and thyroid disease.

Delayed gastric emptying is associated with a variety of symptoms or diseases such as heartburn, irritable bowel syndrome, functional dyspepsia and GERD.

Possible causes of gastroparesis include diabetes, stomach surgery, viral infections, scleroderma and neurological disorders, including Parkinson's disease and spinal-cord disorders. However, in many cases no obvious cause for the gastroparesis is found and hypochlorhydria may be causing the delayed stomach emptying.

Failure of the stomach to empty in a timely manner (delayed gastric emptying), may contribute to GERD (backwashing of acid and bile into the esophagus) in some people. Some studies have shown that this may be due to an increase in stomach pressure which can then overcome the pressure of the lower esophageal sphincter (the valve at the bottom of the esophagus that keeps stomach contents out of the esophagus). Transient lower esophageal sphincter relaxations (opening of the lower esophageal valve) also increase in frequency in response to gastric distention (stretching) and this allows more opportunity for stomach contents to backwash into the esophagus. Still other studies have not found that delayed gastric emptying plays a significant role in GERD in the majority of patients.

Diabetes is the most common known cause. Adrenal and thyroid gland problems can also be a cause although these are infrequent

Symptoms: The usual symptoms of gastroparesis are a feeling of fullness after only a few bites of food, bloating, excessive belching, and nausea. At times there will be a vague, nagging ache in the upper abdomen but usually the pain is not sharp or crampy as might occur with ulcers or a gallbladder attack. There may be vomiting, heartburn, or regurgitation of stomach fluid into the mouth. Medications that reduce or eliminate stomach acid usually don't help much.

Treatment: When gastroparesis is mild, there are usually few food problems. However, if there is marked delay in stomach emptying, then attention to the diet is necessary. Fats, including vegetable oils, normally cause delay in emptying of the stomach, so foods that are high in fat need to be avoided. High fiber foods such as broccoli and cabbage tend to stay in the stomach, so these foods should be restricted when symptoms are severe. Liquids always leave the stomach faster than solid food so liquid type foods such as low-fat milkshakes should be used. Finally, frequent small feedings, 4-6 times a day, are usually more effective than larger meals, 2 or 3 times a day.

Food that is poorly digested can collect in the stomach and form what is called a bezoar. This mass of undigested matter may cause a blockage, preventing the stomach from emptying and result in nausea and pain.

Delayed gastric emptying disorder is generally associated with low blood sugar levels.

Symptoms of delayed gastric emptying may range from mild to severe and include:
• slow digestion
• heartburn
• vomiting
• poor appetite
• stomach spasms
• bloating
• weakness
• weight loss
• sweating
• dizziness
• nausea
• sleepiness
• extreme fatigue.

Causes include:
• diabetes, both types 1 and 2, where high blood glucose levels damage the vagus nerve
• hypoglycemia
• post-viral infections
• smooth muscle diseases such as scleroderma and amyloidosis
• nervous system disorders such as Parkinson's disease
• metabolic disorders such as hypothyroidism.

In gastroparesis, nerves within the stomach are damaged. This slows or stops the muscular contractions (peristalsis) that move food out of the stomach and into the small intestine. Poorly controlled blood sugar increases the risk of damage to these nerves (autonomic neuropathy).

Diabetic gastroparesis also makes it difficult to control your blood sugar due to erratic absorption of nutrients, especially carbohydrates. In turn, uncontrolled blood sugar worsens the neuropathy.

Risk factors for gastroparesis include... use of anticholinergic medication.

An anticholinergic agent is a member of a class of pharmaceutical compounds which serve to reduce the effects mediated by acetylcholine in the central nervous system and peripheral nervous system.

Anticholinergics are typically reversible competitive inhibitors of one of the two types of acetylcholine receptors, and are classified according to the receptors that are affected: antimuscarinic agents operate on the muscarinic acetylcholine receptors, and antinicotinic agents operate on the nicotinic acetylcholine receptors. The majority of anticholinergics are antimuscarinics.

Note: There is a list of drugs with these effects but none are familiar.

Increased Risk of Gallstones

Possible role of a defect in hepatic bilirubin glucuronidation in the initiation of cholesterol gallstones.

Abnormally low activity of hepatic bilirubin UDP-glucuronosyltransferase was found in 25% of 81 unselected patients with gallstones, as compared with only 3% in 35 controls. At the time of cholecystectomy, the stones were taken for analysis in 48 of 81 patients, and a bile sample was obtained in 42 of them. Among the stones, 75% were cholesterol stones, 15% pigment stones, and 10% 'intermediate' stones. Low hepatic conjugating activity was not preferentially associated with a given type of stone... Taking into account the very high frequency of a bilirubin centre in the cholesterol stones (87% of the cases in the present series), it is suggested that the increased proportion in poorly soluble biliary bilirubin monoglucuronide, which was associated with defective conjugation, could act as a trigger for gallstone initiation, regardless of the final composition of the stone.

In Short: 25% of those with gallstones had Gilbert's Syndrome, while only 3% of those without did. 15% of the stones were bilirubin stones, and most of the cholesterol stones had a bilirubin center, meaning that it acted as a trigger for gallstone initiation.

Gilbert's syndrome as a predisposing factor for idiopathic cholelithiasis in children.

The frequency of the (TA)7/(TA)7 promoter genotype of UDP-glucuronosyltransferase gene (UGT1A1) was significantly higher (p<0.05) in a group of 30 children with cholelithiasis than in a control group of 40 healthy children, indicating that this genotype might be an underlying factor for gallstone initiation in otherwise healthy children.

In Short: Gilbert's Syndrome is significantly more prevalent in a group of children with gallstones than without, meaning it could be a causative factor. (Though this doesnt seem to remove the possibility that the children might also have had anemias).

SCIENCE: National Library of Medicine

Analysis of bilirubins in biological fluids by extraction and thin-layer chromatography of the intact tetrapyrroles: application to bile of patients with Gilbert's syndrome, hemolysis, or cholelithiasis.

In duodenal bile of individuals with Gilbert's syndrome (n = 10), the concentration of bilirubin conjugates was comparable to that in healthy adults, but the proportion of bilirubin diglucuronides (52 +/- 8%) was decreased. The concentration of unconjugated bilirubin-IX alpha showed a fair positive correlation with that of bilirubin monoglucuronide and was increased in half of the patients with Gilbert's syndrome.

In Short: It appears those with GS have a similar amount of bilirubin in their bile, though concentrations of unconjugated bilirubin was higher. Bilirubin monoglucurnides are thought to be the ones that create stones.

What Are Gallstones?

The Function of the Gall Bladder
Because fat cannot be dissolved in water, a special system has evolved for its digestion and its absorption through the intestinal wall. Bile is an essential factor in this, since it contains substances that allow fats to be emulsified. It also stimulates the secretion of an enzyme concerned with the breakdown of fats. Bile is secreted by the liver and stored in the gallbladder until needed. When fat is eaten, this stimulates the gallbladder to contract and bile flows down the cystic duct, into the common bile duct and through the ampulla of Vater into the intestine.

Gallstones (Cholelithiasis)
The most common disorder of the biliary tract (gallbladder and bile ducts) is gallstones. Why and how gallstones form is not fully understood, but it is thought that in some cases an abnormality in function causes the gallbladder to remove an excessive amount of water from the bile so that some of its constituents can no longer remain in solution. Gallstones occur very frequently in developed countries and may be associated with eating a diet that is high in fat and refined carbohydrates and low in fiber.

Chronic Cholecystitis (Billary Colic)
The majority of patients with symptoms from their gallstones will suffer from chronic cholecystitis. The attacks are caused by a stone becoming stuck either in the junction of the gallbladder and the bile duct or in the duct itself. The muscle in the wall of both gallbladder and duct contracts in an effort to move the stone and this produces intense pain usually felt under the ribs on the right-hand side of the abdomen. However, the pain may also be felt under the V of the ribs or may extend right across the abdomen and spread around to the back, below the right shoulder blade. The patient may vomit and is usually restless. After several hours, the stone either falls back into the gallbladder or, by virtue of the muscle contractions, is passed down the bile duct and into the intestine. Some patients suffer from a constant dull ache in the upper abdomen and many complain of discomfort and flatulence after eating a fatty meal.

Acute Cholecystitis
Twenty percent of those who develop gallbladder symptoms suffer from this condition, which most frequently affects women between the ages of twenty and forty. Like chronic cholecystitis, it is caused by a stone becoming jammed either in the junction of the gallbladder and duct or in the duct itself, and many patients have previously suffered from binary colic, indigestion, or flatulence. The pain of acute cholecystitis stems from inflammation that is probably caused at first by the chemicals in the bile. However, a bacterial infection then supervenes in 50 percent or more of cases. The pain comes on suddenly and is severe and constant. It is felt across the right and central parts of the upper abdomen and under the right shoulder blade. The patient usually vomits and is quite ill and feverish. If the common bile duct becomes swollen, slight jaundice may occur as bile from the liver is prevented from passing into the intestine and enters the bloodstream instead.

REFERENCE: Wikipedia - Bile

The components of bile:
• Water
• Cholesterol
• Lecithin (a phospholipid)
• Bile pigments (biliruben & biliverden)
• Bile salts (sodium glycocholate & sodium taurocholate)

Bile salts are steroid compounds (deoxycholic and cholic acid), often conjugated with glycine and taurine, and act to some extent as a detergent, helping to emulsify fats (increasing surface area to help enzyme action), and thus aid in their absorption in the small intestine. The most important compounds are the salts of taurocholic acid and deoxycholic acid.

Besides its digestive function, bile serves as the route of excretion for the hemoglobin breakdown product (bilirubin) which gives bile its colour.

REFERENCE: Wikipedia - Gallstones

In medicine, gallstones (choleliths) are crystalline bodies formed within the body by accretion or concretion of normal or abnormal bile components. Cholesterol stones are usually green, but are sometimes white or yellow in color and account for about 80 percent of gallstones. They are made primarily of cholesterol.

Pigment stones are small, dark stones made of bilirubin and calcium salts that are found in bile. They account for the other 20 percent of gallstones. Risk factors for pigment stones include cirrhosis, biliary tract infections, and hereditary blood cell disorders, such as sickle cell anemia. Stones of mixed origin also occur.

Secretion into bile is a major route for eliminating cholesterol. Free cholesterol is virtually insoluble in aqueous solutions, but in bile, it is made soluble by bile acids and lipids like lethicin.

Bile is a liquid secreted by the liver that contains cholesterol, bile salts, and waste products such as bilirubin. Bile salts aid in the digestion of fats. Bile passes out of the liver through the bile ducts and is concentrated and stored in the gallbladder until it is released into the small intestine after a meal to help with fat digestion.

When the bile ducts become blocked, bile accumulates in the liver, and jaundice (yellow color of the skin) develops due to the accumulation of bilirubin in the blood.

The possible causes of a blocked bile duct include:
• Gallstones
• Tumors of the bile ducts or pancreas
• Other tumors that have spread to the biliary system
• Trauma including injury from gallbladder surgery
• Choledochal cysts
• Enlarged nodes in the porta hepatis
• Inflammation of the bile ducts


• Pale-colored stools (caused by lack of bilirubin)
• Dark urine (caused by bilirubin excreted in the urine)
• Jaundice (yellow skin color)
• Itching
• Abdominal pain in the upper right quadrant
• Fever
• Nausea and vomiting

Most gallstones are made up of either cholesterol or bilirubin but not both. Because they range in size from as small as a grain of sand to as large as a golf ball, a gallbladder may contain anywhere from one stone to hundreds. These gallstones may cause problems in the gallbladder or in the bile duct, or they may cause no problems at all.

We are not sure why gallstones happen but we do know that people with high levels of cholesterol in their bile are more likely to develop cholesterol stones and those with high levels of bilirubin are more likely to develop bilirubin stones.

Typical symptoms
• steady pain in the upper abdomen that worsens rapidly and lasts as long as several hours
• pain in the back between the shoulder blades
• pain under the right shoulder
• nausea or vomiting
• abdominal bloating
• recurring intolerance of fatty foods
• colic
• belching
• gas
• indigestion
• sweating
• chills
• low-grade fever
• yellowish color of the skin or whites of the eyes
• clay-colored stools

Table 1. Risk Factors for Cholesterol Gallstone Formation.
1 Increasing age, female sex
2 Ethnicity: Pima Indians, Scandinavians
3 Family history of gallstones on the mother's side
4 Pregnancy
5 Obesity, rapid weight loss, fasting, tube feeding or total parenteral nutrition (TPN)
6 Drugs: fibric acid derivatives, cholesterol-reducing drugs, contraceptive steroids (birth control pills) and postmenopausal estrogen, progesterone, octreotide, ceftriaxone (hormone replacement therapy)
7 Crohn's disease, certain types of surgery involving the digestive system, hyperlipidemia (excess fat in the bloodstream) and diabetes

A Gallstone Attack
As many as one-third of patients with gallstones have symptoms; the remaining two thirds either never know that they have the disease or find out accidentally, for instance by having an X-ray or CT scan for another purpose.3 The most common symptom is called biliary colic; this occurs in 70% to 80% of gallstone sufferers.4 The main feature of biliary colic is severe pain above the stomach area or less frequently in the upper right-hand section of the abdomen. The term biliary colic is a little misleading because the pain is steady, not colicky. A large meal may bring on an attack of biliary colic. More often than not, however, there is no warning or apparent cause.

Biliary colic occurs more commonly at night, often with a sudden onset and increasing intensity over a 15-20 minute period, ending in a steady plateau which can last for several hours. The pain may spread to the area around the right shoulder. Nausea, vomiting and sweating often follow. The pain may gradually go away or decrease, becoming a less severe but persistent abdominal pain. The time period between biliary colic attacks is extremely variable; it may be weeks, months or even years.

When the pain of an attack lasts longer than several hours, it may mean that the gallbladder has become inflamed. This condition, called cholecystitis, can lead to an infection of the gallbladder. Patients with cholecystitis are normally hospitalized for observation, treatment with antibiotics and pain medications, sometimes followed by surgery.5 Elderly people suffering from acute cholecystitis sometimes do not have any pain or fever, and soreness or tenderness in the abdomen may be their only symptom. Jaundice develops in 15% of those with acute cholecystitis.

PERSONAL: Gilberts Web Forums

Between the liver and stomach is a small little sack called the gall bladder. It's purpose is to store bile until you eat. When you put food in your stomach the gall bladder contracts and excretes bile into the stomach to aid in digestion.

Because the gall bladder stores the bile temporarily there is potential for stones to form. Certain chemical conditions have to exist for this to occurr. One of those conditions is excess bilirubin. So you see there "is" a potential side effect to having high bilirubin counts! No one ever tells you that when you have gilberts.

That is why I had to have my gall bladder removed. 28 years of excess bilirubin had caused my gall bladder to fill up with stones. This process usually 50-60 years. Thats why you most often hear of gallstones in elderly people and not younger adults.

Many GS-ers mention that they have abdominal pain, and it always seems to be exactly the same place (above liver, right side, underneath ribs). At the moment it seems like too much of a coincidence to be random or unrelated minor ailments.

I went to see someone on an unrelated matter, but he took one look at my eyes and said I had some kind of liver problem. When I mentioned the abdominal pains he said it could be bilirubin collecting in the gall bladder. This is like having gall stones, but its accumulated bilirubin (instead of whatever gall stones are made of). This is documented in other medical websites.

He gave it a very intensive (and painful!) massage and the pain went away! They have since returned, some days worse than others, but I now massage my abdomen most mornings and it feels like I'm doing some good. Does this sound plausible to others?

I am convinced that the pains that GS sufferers complain of are gall-bladder related

I too had glandular fever and get those exact same pains ALL the time. However, what seems to be different from most GS sufferers is my Gall bladder ultrasound showed up either bubbles or- pools of bile- in the ducts. Has anyone else had this? This seems to fit with belissimo's theory

Black and brown pigment gallstones are morphologically, compositionally, and clinically distinct. Black stones form primarily in the gallbladder in sterile bile and are associated with advanced age, chronic hemolysis, alcoholism, cirrhosis, pancreatitis, and total parenteral nutrition. Brown stones form not only within the gallbladder but also within the intrahepatic and extrahepatic ducts; they are uniformly infected with enteric bacteria and are usually associated with ascending cholangitis. Brown stones are related to juxtapapillary duodenal diverticula and are the predominant type of de novo common bile duct stones. Cholecystectomy is usually curative in black pigment stone disease, whereas stones often recur after cholecystectomy for brown stone disease.

In Short: Apparently there are brown gallstones that form in the gallbladder and liver ducts. These stones are infected with bacteria and cause inflammation.

GS Acting Together With Hemolytic Anemias

Coinheritance of Gilbert Syndrome Increases the Risk for Developing Gallstones in Patients With Hereditary Spherocytosis

The precocious formation of bilirubinate gallstones is the most common complication of hereditary spherocytosis (HS), and the prevention of this problem represents a major impetus for splenectomy in many patients with compensated hemolysis. Because Gilbert syndrome has been considered a risk factor for gallstone formation, there are reasons for postulating that the association of this common inherited disorder of hepatic bilirubin metabolism with HS could increase cholelithiasis.

HEREDITARY SPHEROCYTOSIS (HS) is a common hemolytic anemia and, taking into account the heterogeneity of expression, it has a prevalence of approximately 1:2,000 in Europe and North America... Because the early formation of bilirubinate gallstones is the most common complication occurring in about half of HS patients, the prevention of this problem represents a major impetus for splenectomy in many patients with mild or moderate hemolysis. The pathogenesis of gallstones in HS is related to the high biliary concentration of monoconjugated bilirubin which, in turn, may play a pivotal role in gallstone formation by behaving as a source of unconjugated monohydrogenated bilirubin and as a possible coprecipitant with calcium.

Simultaneous presence of Gilbert syndrome has been described as a possible cause of HS misdiagnosis.

Regardless of their erythrocyte membrane alteration, patients with HS, who coinherited Gilbert syndrome, had an almost 5-fold greater tendency to form gallstones than normal HS patients.

It has recently been reported that after age 40 the rate of myocardial infarction or stroke in HS patients without a spleen is 5.6 times the rate in patients with a spleen and, consequently, a conservative approach to splenectomy in people with HS and mild to moderate anemia has been suggested.

In Short: About half the people with Spherocytosis form gallstones. Those who also inherited Gilbert's Syndrome have a 5-fold greater tendency to form gallstones than those without GS.

Thalassemia minor, the Gilbert mutation, and the risk of gallstones.

ACKGROUND AND OBJECTIVES: Gallstones are a frequent complication of hemolytic anemias. The association with the mutation of the A(TA)nTAA motif of the promoter of the bilirubin UDP-glucuronosyltransferase gene has also been reported to increase the risk of gallstones. We studied the prevalence of cholelithiasis in thalassemia minor and the role of the Gilbert mutation... RESULTS: Total and unconjugated bilirubin were significantly higher in beta-thalassemia heterozygotes. Carriers of thalassemia had a higher prevalence of gallstones (20.3% vs 10.6% OR=2.15). Among the control group, the prevalence of gallstones did not differ significantly in relation to UGT1-A1 genotype, while in women carriers of beta-thalassemia it increased in an allele dose-dependent fashion. As compared to the controls, the odds ratios for the development of gallstones in thalassemic women were 1.68 (95% C.I.: 0.70-4.03) for those who had the normal UGT1-A1 genotype [(TA)6/(TA)6], 2.31 (95% C.I.: 1.06-5.02) for heterozygote carriers of the mutated genotype [(TA)7/(TA)6] and 3.88 (95% C.I.: 1.31-11.55) for those homozygous for the mutated genotype [(TA)7/(TA)7]. INTERPRETATION AND CONCLUSIONS: Thalassemia minor represents a risk factor for cholelithiasis and the Gilbert mutation further increases this risk. This is an additional example of how two genotypes can interact and modify a phenotype.

In Short: The blood disorder Thalassemia minor carries a two-fold risk of developing gallstones, and Gilbert's Syndrome increases that risk.

Hyperbilirubinemia and cholelithiasis in Chinese patients with hemoglobin H disease.

Among 90 Hemoglobin H disease cases, 50 cases suffered from clinically significant jaundice (bilirubin >30 mmol/l), including 14 with severe jaundice (bilirubin >60 mmol/l). Cholelithiasis was found in 38 cases. The incidence is roughly eight times higher than that in background control population but 50% lower than that in beta-thalassemia. The risk of gallstones was related to higher bilirubin levels but not alpha-globin genotype, sex, ferritin, and hemoglobin levels. Homozygotes or double heterozygotes for Gilbert alleles (17.2%), but not heterozgyotes (42.2%), were found to have a significantly increased risk of gallstones and jaundice. However, common Chinese Gilbert syndrome alleles do not completely explain the variable risks.

Note: Cholelithiasis means gallstones.

In Short: Those with Hemoglobin H disease (a form of the Thalassemia blood disorder) have a significantly increased risk of gallstones if they also have Gilbert's Syndrome.

Neurological Impact & Schizophrenia

SCIENCE: National Library of Medicine (PDF)

Inflammatory signalling pathways involved in astroglial activation by unconjugated bilirubin

Moderate to severe hyperbilirubinaemia may lead to UCB deposition in the CNS, causing kernicterus (Hansen 2002; Porter and Dennis 2002; Oh et al. 2003). Kernicterus is a complex clinical and neuropathological syndrome ranging from isolated conditions such as auditory neuropathy and subtle UCB-induced neurological dysfunction to classical kernicterus with athetoid cerebral palsy, impaired upgaze and deafness (Shapiro 2005). It has long been known that only a small number of severe hyperbilirubinaemic newborns show the classical syndrome of kernicterus. In fact, when Schmorl, in 1904, autopsied 120 jaundiced neonates at the time of death, most of the brains (114) exhibited diffuse yellow spots, whereas a more intense colouring in the basal ganglia and the medulla oblongata was observed only in a few (six) (Hansen 2000).

An increased prevalence of schizophrenia in individuals with Gilbert's syndrome and among those who had raised UCB levels in neonatal life has recently been reported (Dalman and Cullberg 1999; Miyaoka et al. 2000). The cause of schizophrenia is unknown, but an association between prenatal exposure to infection and the risk of schizophrenia has been suggested (Gilmore et al. 2004), and the role of cytokines in reducing dendrite development is consistent with the neuropathology of schizophrenia (Grima et al. 2003). It is of interest to note that a short exposure of astrocytes to UCB triggers the release of the pro-inflammatory cytokines tumour necrosis factor (TNF)-a and interleukin (IL)-1b and inhibits IL-6 secretion (Fernandes et al. 2004), a response that is enhanced in younger cell cultures (Falca~o et al. 2005). UCB immunostimulatory and cytotoxic properties are further increased when astrocytes are simultaneously exposed to lipopolysaccharide, suggesting a key role for cytokines in UCB-induced cytotoxicity. Thus, the release of cytokines as a result of UCB immunostimulation may trigger long-term neuropathological effects. Although the mechanisms governing the neurotoxicity of UCB have not been clarified fully, they include the disruption of several cellular vital functions (Rodrigues et al. 2000; Silva et al. 2001a; Brito et al. 2004), alterations to cell membranes (Brito et al. 1996, 2001; Brites et al. 1997; Rodrigues et al. 2002), and a decrease in nerve cell viability as a result of either necrosis or apoptosis (Silva et al. 2001b, 2002; Hankø et al. 2005).

Stimulation of astrocytes by UCB up-regulates cytokine mRNA expression.. Stimulation of astrocytes with UCB induces a time dependent release of cytokines.

Based on previous studies indicating that UCB induces mixed features of cell death in cultured astrocytes (Silva et al. 2001b, 2002; Fernandes et al. 2004; Kumral et al. 2005), we next examined the time course of UCB-induced astroglial cytotoxicity. As shown in Fig. 6(a), UCB induced a time-dependent release of LDH, an indication of loss of cell membrane integrity, with a significant increase over vehicle treated astrocytes from 4 h onwards (p<0.01). As expected, the level of cell death by apoptosis also increased with incubation time (Fig. 6b), with an approximately 1.6-fold increase at 24 h (p<0.01).

A number of previous studies have implicated UCB in mixed features of nerve cell death. Kumral et al. (2005) demonstrated that hyperbilirubinaemic serum induces astroglial cell death in a concentration- and time-dependent manner, whereas Hankø et al. (2005) showed that UCB induces early loss of cell membrane integrity at high concentrations and delayed apoptosis at low concentrations in NT2-N neurones. Moreover, we previously reported that exposure of astrocytes to high concentrations of UCB induced increased levels of cell death (Silva et al. 2001b, 2002). Nevertheless, astroglial death after incubation for 4 h with moderate concentrations of UCB (UCB to HSA molar ratio 0.5) was less than 10% (Fernandes et al. 2004). Our finding of increasing levels of cell death after astrocyte exposure to UCB for longer time periods (Fig. 6) is consistent with these previous reports.

In Short: Moderate to high levels of unconjugated bilirubin (UCB) in the blood may lead to bilirubin being deposited in the central nervous system. Individuals with Gilbert's Syndrome have an increased prevalence of schizophrenia. When astrocytes (a kind of brain cells) are exposed to UCB they stimulate an immune response. This cytokine response reduced dendrite development, which is seen in schizophrenia. UCB disrupts several vital neural cellular functions, alters neural cell membranes, and decreases nerve cell viability.

Astrocytes are sub-type of the glial cells in the brain. They are also known as astrocytic glial cells. Star-shaped, their many arms span all around neurons. They outnumber the neurons ten to one. Astrocytes are classically identified histologically by their expression of glial fibrillary acidic protein (GFAP).

• Structural. A commonly accepted function is to physically structure the brain.
• Metabolic support. A second function is to provide neurons with nutrients such as glucose.
• Blood-brain barrier. The astrocyte end-feet encircling endothelial cells form part of the blood-brain barrier.
• Transmitter reuptake and release. Astrocytes express plasma membrane transporters such as glutamate transporters for several neurotransmitters, including glutamate, ATP and GABA. More recently, astrocytes were shown to release glutamate or ATP in a vesicular, Ca2+-dependent manner.
• Regulation of ion concentration in the extracellular space. Astrocytes express potassium channels at a high density. When neurons are active, they release potassium, increasing its extracellular concentration. Because astrocytes are so permeable to potassium, they rapidly clear its excess accumulation in the extracellular space. If this function is interfered with, the extracellular concentration of potassium will rise, leading to neuronal depolarization by the Goldman equation. Abnormal accumulation of extracellular potassium is well known to result in epileptic neuronal activity.
• Modulation of synaptic transmission. In the supraoptic nucleus of the hypothalamus, rapid changes in astrocyte morphology have been shown to affect heterosynaptic transmission between neurons (Piet et al., Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):2151-5).
• Vasomodulation. Astrocytes may serve as intermediaries in neuronal regulation of blood flow (Parri and Crunelli, Nat Neurosci. 2003 Jan;6(1):5-6).

* General abdominal pain, anxiety, obsessive thinking (e.g: 20 posts on this site! haha), malaise and fatigue are common in GS.

Note: What’s behind the obsessive thinking? Look up


Original Onset and Symptom Triggers


Many people live with GS for the first part of their lives with no symptoms. For some people it comes on gradually around age 24-30. For others there is a trigger that sets it off, that makes it worse in a continuous way for a long period of time. The trigger changes it from something that is easy to ignore to something that is a constant disruption. Further triggers can increase the severity of symptoms through time.

Several triggers are often repeated when discussing the onset of GS symptoms- antibiotics, viral infections (especially the Epstein-Barr virus), hepatitis vaccinations, and food poisoning. There's also the idea out there that it comes on due to hormonal changes, which is an idea that interests me - I wonder if we couldnt alter hormone levels in some way to bring us the protection from symptoms we had when we were younger.

Four things happened around the time that things initially started getting bad for me:

1) I reached my mid-20s, which appears to be a common time for GS to start showing itself
2) I was immunized for Hepatitis among other things in preparation for international travel
3) A couple weeks later I was in the presence of someone who turned yellow and passed out from Hepatitis.
4) A week later I came down with severe food poisoning. The pain was excruciating and I was vomiting and had diarrhea like never before.

After taking nasal steroids to deal with an unusually bad reaction to pollen last spring, I developed a sinus infection that turned into Strep Throat a week later. I went to the doctor and got a shot of antibiotics (Rocephrin) and a shot of cortisone (Depomedrol). I was then put on a 10 day course of Omnicef. My sinuses and throat soon felt better but I also suffered a sudden increase in Gilbert's symptoms, from which I havent really fully recovered months later aside from a few good days here and there.

Triggers - Hormones (Age 24-30), Steroids

The syndrome is usually detected in adolescents and young adults, most commonly in male persons; the possibility that testosterone inhibits whereas estrogen and progesterone augment the action of UDPglucuronyl transferase may provide the explanation.

My symptoms actually started when I was a young seemed to be set in motion by steroidal allergy shots I was getting in the summer

Had blood tests back today with high levels of Bilrubin (25) and everything else was normal. I simply got up one day exactly 3 weeks ago felt dizzy and fatigued and slept for 2 days, have had a doctor (my father) think that it it is a stomach ulcer and have been on Proton Pump Inhibitors and antibiotics for about a week. I haven't felt much better and very worried because I use to run for an hour a day and was a semi professional squash player. I am getting very depressed my work is suffering and don't know if I can live the rest of my life like this, I am only 25!

i got diagnosed the GS in -94. I'm a 26 year old guy from Sweden. I'm used to sports(extreme) like surfing and skateboarding, but this fatigue is getting on my back. I actually didn't experience any until like 2 years ago even though diagnosed almost 8 years back. In the mornings i'm dizzy and sometimes nausius(can't spell..) and it takes me about an hour to get back to normal each morning. I usually get really tired at noon or in the afternoon and HAVE to take a nap for about an hour or so.

I was diagnosed at 17 originally as Hepatitis and after about a month of blood tests and a specialist I was diagnosed with GS...It has mostly been dormant (except for youthful drinking binges) until I hit 30 and its been high maintenance since..I'm 32 now..

Triggers - Antibiotics

I have allergic rhinitis and the ENT I was seeing prescribed me 14 days course of Augementin, 10 days later I developed chest pains, went to the doctor who said it has to be esophagus (food pipe) that is inflamed due to antibiotics being too strong so I stopped. A day or 2 later I began to feel extremely fatigue and sleepy, thought was reaction to the new medicine I was given for the food pipe but after I stopped that too, the fatigue just won't go away so I went sent for a liver FT, the results came with bilirubin 21 and AST/ALT raised (the paper that comes with augmentin says that in people with hepatic reaction temp ALT/AST rise may occur), the next week I had a repeated blood test done, bilirubin 26, ALT/AST still raised but the week after only the bilirubin was elevated at 25. Liver scan was OK so the gastro told me I have GS.

I am now on antibiotics again as I just had my last 2 wisdom teeth removed so the dentist is scared of the infection, etc and put me on 2 antibiotics (that is Amox and Metro), the total comes up to 12 a day plus paracetamol for pain but considering that I cannot eat much due to the pain and having to take antibiotics on almost empty stomach I had vomiting and now cut down just to amox. I am feeling "blur" and sleepy all the time again, guess must be the antibiotics effect on the liver again but I have no choice now.

irina (later post)
Elevated ALT/AST was allergic reaction to augmentin and it brought on the onset of my GS (I am 25 female, I have lost almost 10 kgs during that period of time). My fatigue has gone away after a few weeks then and I was more or less ok except for panic attacks and depression (I did not have those before all this ordeal with GS). I had another LFT done in Feb, all ok except bilirubin which was 28. Anyway, I had wisdom teeth surgery done a few weeks back and had to take amoxicillin for 10 days to prevent infection (I am taking milk thistle tablets too), all seemed ok.. however my son passed the flu to me (cough, blocked nose, very red throat but no fever) and the doc put me on a 3 day amoxicillin course (6 x 250mg capsules a day, I did not complete the course, I am extremely scared of taking antibiotics now after what Augmentin has done), I am not sure if that was due to the medicine or the flu but my sleepiness came back, i wake up in the morning like if I had never slept and it lasts the whole day... my head feels a bit blur too..

Rezan Lebbe
am still comming to terms with gilberts. but am sure also that my gilberts was brought on by minocycline . same stuff that you were on shaun . my bilirubin count was 37 in december and went down to 16 in march which is apparently normal but before the minocycline i was never this bad

I've now had GS confirmed... I've been taking Minocycline for just over 4 months (I know that seems a lot - but most anti-acne treatments are long-term)... I've been shocked at how tired and listless I've been feeling. Any exercise seems to leave me exhausted, I have an almost constant headache, and my yellow eyes hurt a little too... I already feel a little better since coming off the drugs - but my eyes are still yellow, and I still have headaches.... given what you've said, as well as the fact that another course of anti-acne medication (Erythromycine) has since caused my symptoms to return, I'm now far more sure it was the drugs that were responsible... The common theme triggering my 'attacks' in the last year has been some sort of medication. First the anti-acne antibiotics turned me jaundiced, and by the time I was diagnosed with GS last April, led me to become exhausted and suffer chronic headaches too. Then I came off the antibiotics, and steadily got better. Then I tried a different type of antibiotic in June; and within days, my jaundice and fatigue had returned. Rest assured, I'm not trying those things again! The same thing happened when I saw a homeopath last summer: the milk thistle and antioxidant he prescribed made me feel dreadful (and I'd even wake up looking like a banana). So I stopped taking those too.

Shaun (later post)
I came off the antibiotics (my useless doc thought I should stay on them), and my bilirubin, after peaking at 86, slowly fell back before levelling out at 40. So most of my symptoms (tiredness, yellow eyes, etc) were reduced, but didn't completely go away. Then I was stupid enough to try some different antibiotics (Erythromycine), and after a few days, the problem returned. That was about 2 weeks ago. Unfortunately, I'm still suffering - in fact, if anything, I'm feeling weaker, and have gone jaundiced the last day or so.

I've just been prescribed 10 days of Augmentin. My GS symptoms : nauseau, dizziness, fatigue, etc, were more or less in check but since I took these antibiotics they've come back with a vengeance. I'm taking milk-thistle again and it definitely provides relief.

Me: It's difficult to determine whether it is the virus or the antibiotic that is the trigger.

Yet there is evidence, even in my own experience, that antibiotics are themselves a cause (in addition to illness), as there are some cases of preventative antibiotics where there is no illness causing symptoms to flare up. My own experience is that I came down with strep throat, got a course of antibiotics and a cortisone shot which cleared it up, but then afterwards I became far more sensitive to carbs - they hit me harder with fatigue, food coma, and brain fog than before the antibiotics. Could this be a candida reaction? Just GS? I've also seen reports that cortisone/steroids can set off symptoms as well. I had that at the same time as my antibiotics shot.

Triggers - Epstein Barr Virus (Mononucleosis/Glandular Fever)


Glandular Fever is also known as Infectious Mononucleosis and is a viral infection caused by the Epstein-Barr virus. How is glandular fever treated? Is it through antibiotics? And if so, how long is the course? If this is treated by antibiotics, then it could be a trigger leading to a candida problem, as antibiotics often result in candida overgrowth.

Liver involvement is frequent in the immunocompetent child along the course of infectious mononucleosis (IM) and is typically characterized by mild to moderate and transient increase of serum aminotransferases... During Spring 2002 an epidemic of IM occurred in Valsesia, an alpine valley in the northwest of Italy; at least 200 cases were referred to family physicians or pediatricians, and 10 of these were hospitalized thereafter because of fever persisting for >5 days.

TABLE 1. Characteristics of hospitalized patients*
Patient Age (yr) ALT Value AST Value GT Value Bilirubin Value UDPGT1 Status
1 2 26 21 8 0.80 TA6/TA6
2 2.3 29 12 10 0.25 TA6/TA6
3 5.2 30 21 7 0.20 TA6/TA6
4 12.4 15 9 6 0.30 TA6/TA6
5 12.4 19 13 6 0.35 TA6/TA7
6 4.8 520 411 111 12.5 TA6/TA7
7 5.1 182 236 141 0.25 TA6/TA7
8 10 396 282 124 0.97 TA6/TA6
9 15.8 80 105 117 1.95 TA7/TA7
10 15.9 177 177 116 2.30 TA7/TA7

* ALT n.v., <39 units/l; AST n.v, < 29 units/l; GT n.v, 5 to 35 units/l; bilirubin n.v., <1.1 units/l; UDPGT1 normal status: TA6/TA6; heterozygous: TA6/TA7; GS: TA7/TA7
ALT, alanine aminotransferase; AST, aspartate aminotransferase; GT, gamma-glutamyltransferase; Neg, negative; n.v., normal value.

Although this study involved only a few selected pediatric patients hospitalized for prolonged fever during the course of IM, nevertheless it could be postulated from these data that Epstein-Barr virus, alone or in combination with other factors, such as drugs, may impair liver function mostly in individuals carrying either homozygosis TA7/TA7 (GS) or heterozygosis TA6/TA7 for the UDPGT1 gene promoter. A more severe clinical course of IM could then be the expected consequence of this genetic feature. Indeed if the genic frequencies were independent of the liver involvement, then the same clinical features should be recovered in the first group of patients.

My question to all of you is due to a suspicion I have. 10 years ago I came down with Glandular Fever/Mononucleosis very badly. It is since this time I have suffered the abdominal pain and all these seemingly unrelated minor ailments that together are becoming debilitating.

I have suffered from GS since a bout of glandular fever 16 years ago, but it was years before a got a diagnosis.

I, too was diagnosed after a prolonged viral infection. I had a fever for 2 1/2 months, was extremely pale, and so fatigued they thought I must have Epstein-Barr. Eight months, and three doctors later, I was finally diagnosed with Gilbert's

I was refered to a private specialist who diagnosed me with GS. He didn't really give me any advice apart from saying that it may cause some fatigue, but that it hasn't been proven and that it's not life threatening. He never discussed anything about taking supplements and I felt as if I was left to flounder. He also found from the blood tests that I had had glandular fever, which I wasn't aware of. I've been feeling increasingly low and more and more tired all the time

I've had GS since 1990........and also glandular fever, two bouts of meningitis all within a one year period. Was diagnosed with chronic fatigue since then and am still now battling with my health (inc. chronic fatigue)... Apparently, the body should have cleared the virus by now......but hasn't.....and yet, I now know that GS also predisposes a body to slow recovery from a virus, therefore, I think GS predisposes us to chronic fatigue syndrome, but my Live Blood Test results prove that it is also viral..and not JUST GS.

Triggers - Viral

Wild coyote
I was diagnosed by accident last year after an extended period of illness caused by a viral infection… i was suffering from flu and had 2 miss my exams. In saw my doctor 2 get a letter excusing me and was told it would last for 7-10 days and just 2 stay in bed. After 2 weeks i was getting worse and eventually collapsed, only 2 wake up in the back of an ambulance. 2 days in hospital later i was told that the Flu had led to a bacterial infection, which in turn had led to an, as yet still unidentified, viral infection.

I was diagnosed 10 years ago with post-viral fatigue syndrome (ME). The blood tests came up with GS but my GP said it was nothing to worry about. 10 years later, after recovering twice and now relapsed a bit again, I went to see a Harley Street ME specialist called Dr Hyams. He said that people with GS have a suceptibility to ME and that the Brainfog is caused by the liver being unable to detoxify properly. So, I was wondering if all you people with GS got ill all of a sudden like I did with dizziness,fatigue, concentration problems, ie ME symptoms

Flu-like beginning with dizziness and fatigue etc IS DEFINITELY classic ME/CFS/Post-viral fatigue/Yuppie flu or what ever you want to call it. Did you get worse or do you get worse when you exercise or do the gardening or heavy work etc? Thats is also classic ME symptoms.

Some researchers are looking at the immune system and others are looking at the brain. I myself feel that it is a dysregulated Brain. They know the Hypothalamus (the Limbic system which regulates sleep, heat control and hormonal function) is affected.

I've been diagnosed GS for the last month but went to him about a year ago after a flu-like illness suffering extreme fatigue, dizziness, reflux, brainfog

he did mention gilberts' disease----which was ironic. SO, in consideration of CFS/ME being of viral origin, it may be poisoning the liver or over taxing it to contribute to the elevated levels of bilirubin. The chicken or the egg, and definitely not benign. My descent into CFS/ME is that typical flu infection that most people talk about, but I had the extra baggage and blood tests.

For me it all started with a viral infection that was brought to my attention when I had a panic attack on a Friday night and it lasted all weekend. I went to my Dr. on Monday and she found that I had a fever and elevated bilirubin (but I was not diagnosed at this time). After about 3 months, when the viral infection wasn't as debilitating as it had been, I was still anxious when i was out. It became so that I was fearful of going out, becuase I knew I'd feel awful. I have never suffered from anxiety or panic attacks in the past... I personally avoided social situations for many months. As I got healthier after the viral infection, I noticed that I was able to do more and more - like sit through a dinner in a restaurant with my boyfriend... Interestingly enough, a few sips of alcohol doesn't relax me, it actually gets me anxious, and then gets me completely drunk.

I had NEVER been stricken with anxiety or panic attacks, then suddenly I get a viral illness and had a hellacious panic attack and then several more. Got to the point in went in for testing for adrenal problems and was diagnosed with GS. There has to be a connection because I had never been anxious prior to that. I too have spent a lot time avoiding certain social situations, but have to go and do stuff I don't want to because of work. It is better now but still that same old anxiety/social phobia can crop up and embarrass me. This has really changed my life and it is NOT mental in origin, but truly came from some physical origin like the virus I believe... Alcohol has the same effect on me you describe and tends to make my heart race.

I had a similar experience. I would have described myself as confident before contracting a viral infection in 1991. It started with a sore throat followed by a very high temperature. Nothing was found following tests but I was left in a state that at times was best described as agoraphobic. I had aching in every muscle that left them sore to touch and even made lying down a problem. I lost two stones in weight over ten days and sleep was a problem as I could not lie down for long. The next six months left me with a nervous breakdown. I went to a health clinic to recuperate and following blood tests I discovered the high Bilirubin showing 72 at the time.

They tried me on Antidepressants with devastating results for me. I stopped taking them... All my senses seemed super sensitive and I suffered anxiety of a type I had never experienced before. I used a product called Api Regis Royal Jelly for a period of time and still turn to this at times. It seems to do something no other product can in relation to restoring me to a normal state and it also helps with the fatigue. I know it is full of a range of the B vitamin and there is a link with the nervous system and deficiencies in B vitamins. It is the fresh Royal Jelly and is suspended in a medicinal wine. Liquid seem better than tablets for me in most treatments.

Note: This sounds like LSD.. the connection to schizophrenia might be relevant here.

I suffered from depression and anxiety after my viral infection / gastroenteritis (the doctors really didnt know what was wrong with me). All I know is I continued to feel extremely ill and unable to eat anything for a long time and lost lots of weight. I think it was perhaps because of the way I was feeling and all the tests that were being carried out and coming back as negative that made me feel so low... I have to say that I too had never experienced panic attacks before becoming ill but I got to the stage where I felt uncomfortable in any public place including out shopping which i'd had no problem with before. I'd feel all hot and clammy and my heart would be pounding like it was going to leap out of my chest and i'd feel like i couldnt breathe properly.

Triggers - Food Poisoning

I'm 23 and during a holiday to Malta I became ill, was seriously dehydrated and had to goto hospital... So as far as I can tell I began to have GS symptoms after being extremely ill originally with food poisoning on holiday. I am now taking ...anti-emetic drugs (domperidone/motilium), anti-acid (nizatidine) and also antidepressants (lofepramine)... since taking these I have begun to feel ALOT better but still worry that once Im taken off the anti sickness tablets the nausea will return.

JodieToadie (a month later)
I've been feeling ok recently ("touch wood") I don't take the domperidone any longer but still keep some aside incase I need them again. I am still taking the antidepressants as prescribed but still unconvinced that they are the solution to the problem.

Triggers - Hepatitis Vaccinations

Why have I got it now I ask myself. 33 years of age. I had an injection for Hepititus to go on holiday a few years back but never went and my liver inflamed. I wondered whether that started it off... I have started to take Milk Thistle, any other suggestions...

naomi block
Sarah - I also wonder why I 'got' it now, I used to suffer very badly from cold sores and took some treatment for it from doc and herbal, I think this really stressed my liver, although doc would never admit it. The medicine they gave me was not good for liver... the herb I used called Chapparal, I have since discovered, can cause drug induced hepititis. The thing is that there's no answer and I just get on the best I can, but would like not to feel constantly just 'not really well'.

I've had Gilberts for 9 years now, diagnosed after a bad bout of gastric flu. It would only come on when I was stressed or ill. The rest of the time I'd have no symptoms and my eyes were pearl white! However, ever since I had the Hepatitis vaccine in October 2005 I've been Mr. Yellow.

It has been a stressfull time for me of late with life and I put my recent high bile levels since then down to that, toxic feelings and occasional energyless-ness as well. Having read this site I'm not so sure! It is really odd how this all started after I had the vaccine in October! GS never used to bother me until I had this damn vaccine, I'm sure that's what's caused all this.


My problems kicked in approximately 5 years ago, when I was 26. About 5 1/2 years ago I did some international traveling and was vaccinated for hepatitis before I left. Not long after this I suffered a bout of extremely bad food poisoning. This is also the approximate age of onset for a lot of people. So it could have been any of these things for me.


Connections To Other Problems

Hypothyroidism (major section)

There are connections between Gilbert's Syndrome and hypothyroidism in ALMOST EVERY AREA I've investigated. They share many symptoms and interact in many ways that this section has its own page. Learn more about Gilbert's Syndrome and Hypothyroidism.

Chronic Fatigue Syndrome / ME (major section)

People with GS are four times more likely to have Chronic Fatigue Syndrome (also known as ME or Post-Viral Fatigue Syndrome) than others. Due to the numerous connections and similarity in symptoms, this also has a page of its own. Learn more about Gilbert's Syndrome and Chronic Fatigue Syndrome.

Candida (major section)

There is evidence that candida may be involved with and bolstered by the effects of Gilbert's Syndrome. Learn more about Gilbert's Syndrome and Candida.


Mercury Toxicity

PERSONAL: Gilberts Web Forums

Snail Trailer
i was researching mercury issues and came across one person's story who is convinced that his GS is caused by mercury poisoning! apparently heavy metals interfere with the bilirubin processing of the liver and compromise its function.
My GS erupted last year after my dentist removed a filling without taking any precautions. I have brought the bilirubin down from its highest level of 2.7 to 1.5 through diet, but I now have chronic fatigue. My main symptoms are fatigue, underactive thyroid, upset body clock - I wake up every morning at 4.30am without fail - hot flashes, candida, muscle twitches and food sensitivities. As the bilirubin has come down so much, I conclude that all these symptoms are due to mercury toxicity, caused not just by the filling removal last year, but also 30-odd years of leaking mercury amalgams in my teeth, and a regular tuna-fish habit. I am now working to detox mercury and start removing my fillings soon. My dentist has warned me that it will be a very slow procedure - to do it quickly will overwhelm the liver.
To fully understand the impact of mercury on the liver, you need to read This is the best one I have come across, and explains the relationship between mercury, muscles twitches, acidity, the detoxification pathways (of which number two is sluggish in people with GS). I first noticed muscles twitches two years ago and went to see a neurologist about it, who found nothing wrong. I now know that this was due to my body becoming increasingly acid as the mercury burden built up, and the body pulls calcium from the bones to try to alkalinise its environment. It also explains that people with mercury fillings are in a fixed acidic state, which won't resolve until the fillings are removed and mercury is detoxed.
I am now detoxing with NDF, with good results.
Another link by the man considered an expert in mercury toxicity, who also had it himself.

I have had a hair analysis which showed classic mercury toxicity - high mercury levels, low thyroid and low adrenal function. I have also had a vega analysis which diagnosed medium severe mercury toxicity. My symptoms (candida, hypoglycaemia, hypothyroidism, hypoadrenalism, depression, fatigue) are typical for mercury toxicity.

Berbanky - we are doing the same thing. I am also getting to grips with my health issues which started after a dentist removed a mercury amalgam two years ago without taking any precautions. The release of mercury vapour pitched me full speed into Gilberts, candida, hypothyroidism and mercury toxicity - though the doctors would label it chronic fatigue. All these are issues that Carl Tuttle (runagain) also had to deal with.

I have learned a huge amount about hypothyroidism, mercury, the liver pathways, candida and treatments from Andy Cutler's book Amalgam Illness, available from Amazon. Expensive but really worth it for identifying and treating these issues. He states that the efficacy of the glucorinidation pathway (the culprit in Gilberts people) can be increased by raising thyroid hormones, ie that the Gilberts can be exacerbated by hypothyroidism, rather than Gilberts causing hypothyroidism.

Celiac Disease (Gluten Sensitivity)

I found out a few years ago I have Celiac which is gluten sensitivity, and I have gilbert's also. There is a big overlap in symptoms. A lot of people, including a good friend of mine are diagnosed with irritable bowel and often find out is Celiac disease. Your alternating bowel symptoms is one of the ways it can be expressed.  My friend suffered all of his life and went to numerous doctors who kept telling him it was just IBS, and when I shared information on celiac with him he recognized himself and went on the gluten free diet and told me he has never felt better and wished he could have known when he was much younger.

Celiac disease is an auto-immune disorder of the digestive system that occurs in genetically-predisposed individuals. It is characterised by damage or flattening to all or part of the villi lining the small intestine, which interferes with the absorption of nutrients. This damage is caused by eating anything with gluten (gliadin), a protein found in wheat, rye, and barley (as hordein).

The diverse range of coeliac disease symptoms may make it difficult to diagnose. There are over two hundred symptoms that have been identified; not all people have the same symptoms; some people have no symptoms at all; and the symptoms may mimic other diseases. Comprehensive lists are available.[1] [2].

Gastrointestinal or digestive problems occur in some coeliacs. It used to be thought that all coeliacs had diarrhea, weight loss, and nutritional deficiencies, but it is now known that only a small percentage have these symptoms. The wide range of digestive symptoms include everything from canker sores to diarrhea to constipation to nausea. Many of the symptoms may mimic other diseases such as irritable bowel syndrome, reflux, or even Crohn's disease and coeliac may be misdiagnosed as any of these. Other symptoms that may occur are bulky, pale, offensive-smelling stools which may float in the toilet bowl, excess flatulence, infrequent, minor rectal bleeding, or persistent pain in the abdomen.

Some symptoms appear to be caused because the villi are unable to absorb nutrients. Some examples are osteoporosis, damage to teeth enamel, anemia, fatigue, rapid or unexplained weight loss, overweight, failure to thrive or stunted growth in children, etc. Yet other symptoms appear to be emotional, such as depression and irritability. Dermatitis herpetiformis is an itchy blistering skin disease that occurs in some coeliacs and is considered to be an external manifestation of coeliac disease.

I've not heard of a link, but I happen to have wheat well as other grains, especially with gluten.(I found out by having a bowel biopsy).Don't know if that's just a coincidence though.However, in my case it IS related to IBS, for which my surgeon/specialist does not know the initial cause, and which does seem to be linked to GS.
The only grain I feel GOOD eating is Buckwheat, which is unrelated to wheat, and doesn't contain gluten either. Other than that I can tolerate small amounts of rice.

I got ill two years ago and initially was diagnosed with intestinal yeast (following strong antibiotics). A yeast free diet which included giving up bread helped tremendously. Since then, after much research I have found I sensitive to gluten/dairy/yeast. Only recently, working with a Naturopath Doctor, I learn that my Bilirubin which was high since age 20 (possibly earlier) could be related to this recent illness. I have since found two other liver tests have crept up to the top of the range, however these might be related to the gluten as I found information on the site explaining the relationship. A gluten/dairy/yeast free diet has made a big difference to my well being. Gluten sensitivity is also know as Celiac disease. Your body creates antibodies to any of the grains from the wheat family.

I have also had practically all of the symptoms described in the other emails. Most have cleared up since starting on a gluten/dairy/yeast free diet. Do check on the site as it gives a long list of symptoms, and you might want to research Celiac/Wheat allergies.
I have not had any panic attacks, sore throats, sinus problems, foggy/blurry eyes and more since the change in diet. However, I do still get the under rib discomfort sometimes pain. I think this may be the GS, and I really am wondering if it is related to Celiac. I have only been eating this new diet since June and they say you have to be gluten free for a good period of time up to two years for some people.
A lot of people who are told the have IBS, actually have Celiac disease. The difficulty is the blood test for Celiac does not pick everyone up. I found a site called www., they do a stool test and gene tests. Today I read the Italians who are the experts on Celiac are coming up with a new test similar to Dr. Fine's which reassures me Dr. Fine is quite progressive and dependable. Some research is showing that 1 in 33 people have this problem. It is an area which research has only begun in earnest in the last few years, and their is no medication to fix it so the funding by the pharmaceutical companies will be missing. The cure is in what you eat and don't eat.

Connections - Irritable Bowel Syndrome (IBS)

The connection between Gilbert's Syndrome and Irritable Bowel Syndrome is most likely due to gastroparesis, which has been found to be connected with GS. IBS is diagnosed when the real source of gastrointestinal problems cant be found. For more information on gastroparesis, see the section on Symptoms.

I always complained of stomach pains etc and my list went on and so did my visits to the doctors. I was told for many years that gs has no symptoms and I only have ibs so get on with it. I didnt get on with it, after trying to convince myself nothing was wrong with me, I decided not to give up. I was eventually given a colonoscopy and was told I actually have crohns disease (inflammatory bowel disease).

I was diagnosed with Ulcerative Colitis last year after 25+ years having GS. My UC seems to have settled down with medication (Mesalazine - Asacol).

I was diagnosed with IBS a couple months ago after having symptoms for several years (6/7). I was just diagnosed a couple weeks ago with GS, after a year of tests

I have had gilbert's for quite some time now.. I do find that if I have a sudden change in my diet (missing a meal, or eating a lot of junk food) IBS becomes more of a factor for me. I will get stomach pains, get bouts of diarrea with mucus in it, after a couple of rounds of that i will feel much better and i will have normal stomach functions (for the most part).. the GS and IBS seem to go in a cycle for me.. I also tend to feel these symptoms much more if nervous or stressed out.


Yes I have IBS and Gilbert’s too and never linked the 2 until today
I have Gilbert’s and IBS too.
I have IBS, Gilbert`s syndrome & I get magraine`s.
Has IBS and GS.
I have both GS and IBS as well.
I too have discovered I have IBS and GS.
i am 22 year old gs sufferer i have ibs too.
I have IBS and Gilbert's as well. It seems that the IBS is worse when the other symptoms of Gilbert's are at their peak.
I have GS & IBS, too.
I get IBS so bad I literally have passed out in the bathroom from nausea and pain. I've noticed pain under right ribs a few days before one of these attacks, followed by needing a couple of days to recover from one of these attacks.Things that make me more suseptable, I think, are: lack of regular water, bread (especially white), pasta and chocolate (definitely).
I am lucky in that I have a doctor who actually believes that GS can have symptoms. When I was first diagnosed (having gone in for some digestive problems), she indicated that in her experience people with GS very frequently suffered digestive problems and a high percentage were classified as having IBS. IBS is one of these catch-all classifications for what are undoubtedly a variety of bowel disorders.

For me, all of my GS symptoms are definitely associated with digestive/bowel problems. The panic attacks that I have experienced were undoubtedly a side effect of digestive system problems (wierd but true). The fatigue that I have experienced is not some general problem, but a very specific, profound weakness that comes only at the height of the digestive problems.
I have GS and IBS(constipation) and migraines,depression,anti-social,shy, tiredness,weekness yellow eyes,nausea sensitivity to light but also dislike heat.I also have low blood pressure.The doctors always told me that was good.I also have a lack of desire or motivation to exercise.I have not lost weight but gained weight(probably due to the lack of exercise)but I always seem to be hungry.I think I'm possibly compensating for the low energy and fatigue by eating more food to give me more energy… Also does anyone suffer from sinus pressure or barometric pressure problems if not maybe its just me(Maybe its just connected to the migraines)… the corners of my eyes are clearly yellow.


Connections - Various


Led by Dan A. Oren, associate professor of psychiatry at Yale, the first investigation of its kind has revealed that patients affected with SAD display lower nighttime levels of bilirubin, a bile pigment found in the blood, when compared to age- and gender-matched healthy volunteers. Similarly, SAD patients exposed to a light source, a common treatment for the disorder, demonstrated increased levels of bilirubin.
Excess bilirubin may trigger seasonal depression, a disorder that affects up to 10 percent of people in the northern United States. More common in females, SAD only afflicts its sufferers during the winter months, and is characterized by lack of energy, decreased interest in work, carbohydrate cravings, social withdrawal, and lethargic movement.
The study also suggests that light is an effective treatment for the disorder because of its ability to lower bilirubin levels.

Im using St Johns Wort. As a student of neuropharmacology I know that it is generally used to treat depression esp SAD. Research of Dr Dan Oren at Harvard has shown that SAD can be caused by excessive bilirubin. With my GS I also suffer from SAD (Seasonal Affective Disorder). The idea behind it is basically that in the winter there is a lot less UV light to break down the bilirubin, which directly affects the brain to cause depression.

Leaky Gut Syndrome

In researching some information about Psoriasis I read an article relating to a link with Leaky Gut Syndrome. Some very interesting aspects were raised relating to the taxing of the Liver when Leaky Gut Syndrome is present. Some theories link Leaky Gut Syndrome to many of the conditions reported on this site such as CFS, Fybromyalgia, food allergies, stomach discomfort, etc.

Variegate Porphyria

* VERY RARELY......GS patients develop a condition that RESEMBLES Variegate Porphyria

Again, don't panic, this is extremely rare, but I just found this out and thought it's best to share any findings with you all. Variegate Porphyria symptoms can include: extremely fragile skin (burns extremely easily in the sun....not just redness but blisters after only a short time), skin so fragile it tears/cuts easily and scars,very severe abdominal pain that can include vomiting and even psychological disturbances at the time, and sometimes even seisures.

* I repeat that all this is EXTREMELY RARE !!!(IBS symptoms are common in GS, and don't mean you have the above disorder)

*** Porphyrias are a group of disorders that ALSO have a lack of an hepatic enzyme (in the case above: protoporphyrinogen oxidase), just as Gilbert's Syndrome sufferers lack glucose transferase, but the difference lies in that porphyrias have to do with the BUILDING up of the red blood cells in the Heme Cycle, while GS (and other disorders) have to do with the BREAKING down.Interestingly, treatment for porphyria includes no sun exposure and relies in lots of carbohydrates....while many people with GS find sunlight and high protein diets help!!!

Vision Problems

Liver malfunction generally can lead to eye problems if the liver is not breaking down sugars - in particular fructose which can be converted in the liver to sorbitol - this leads to reduced vision.


My doctor told me that I have enlarged red blood cells so she checked the usual reasons (vitamin and mineral deficiencies) but they came back normal so she sent me to a hematologist. He also ruled out the usual causes like anemia and it too was normal. He was concerned so he had me go through a bone marrow biopsy to check for pre-leukemia. It too was normal so he concluded that these enlarged red blood cells (called macrocytosis) was due to my Gilberts.

naomi block
tunedee, that's really weird, my brother and I both have been diagnosed with Gilberts but my sister went to the doc's complaining of dizzy spells and had her blood checked only to be told she had enlarged red blood cells... I wonder what would happen if she too was checked for Gilberts, she never seems to be that well.


I did possibly find a link between pots (which gives me tremors, dizziness and heart palps) and gilberts, which is also interesting
Hally m
I am interested in looking further into POTS because, apart from the dizziness, fatigue, digestion etc, I suffer all the problems with standing, temperature regulation and what looks like blood pooling in the legs.

Postural orthostatic tachycardia syndrome (or POTS) is a condition of orthostatic intolerance in which a change from the supine position to an upright position causes an abnormally-high increase in heart rate, often, but not always accompanied by a sharp fall in blood pressure.

The syndrome was identified as such by Schondorf and Low in 1993. Similar symptoms were collectively described as "idiopathic hypovolemia" by Fouad in 1986.

Symptoms include a sudden increase in heart rate upon standing, often accompanied by hypotension, and associated with dizziness, fatigue, and nausea. About 80 percent of patients diagnosed with POTS are female and of menstruating age.

The causes of POTS are not fully known, since the term describes a collection of symptoms rather than a disease. It is generally believed to be a case of dysautonomia. Its onset is sometimes associated with an inflammatory condition such as a viral infection. An overlap of symptoms with chronic fatigue syndrome may suggest a pathological overlap in some cases. The condition is often diagnosed using a tilt table test.

Adrenal Fatigue

I recently went to a chiropractor who told me that I have extreme adrenal exhaustion. For those of you who have fibromyalgia or CFS-like might want to check into this. She checked my blood pressure lying & standing....and when I stood it dropped abnormally low. She said my symptoms were consistent with adrenal exhaustion, as well as my eyes dilating when they should constrict and vice versa. Anyways, she gave me a B Complex vitamin by Nutri West with inositol, PABA, biotin and some other stuff that helps with stress/adrenals/hypoglycemia/aches....etc. It has helped a lot....She also is having me start up three daily juices by Oasis called Metagreens, Metaberry and Aloe Gold. It basically is a bunch of herbs, vitamins and antioxidants which help you to detox. I will let you know if that helps, but I do know that the B Complex has made a huge difference in my anxiety levels, palpitations, blood sugar, aches, and fatigue.
I am also on adrenal meds - glandulars as well as replacement cortisol, and they have made a big difference. I have CFS - or rather hypothyroidism and hypoadrenalism.

Androgen Levels

PERSONAL: Gilberts Web Forums

The reason I ask is because I believe Gilberts Syndrome may in fact be related to androgens (hormones). And if any of you males follow male pattern hair loss, we know that DHT is the primary cause of hairloss. I have noticed a startling pattern among Gilbert's Syndrome patients, and hairloss.

Currently, I am taking finasteride for hairloss (Propecia, Proscar) and guess what...

Gilbert's Syndrome has almost completely dissappeared.


PERSONAL: Gilberts Web Forums

Shortly after I was told I had large fibroids and would need to have a hysterectomy. I have spent the last two years arguing with my gynaecologist, and have now been referred to a different one who is prepared to offer me less drastic treatment. So of course I thought my IBS-type problems must be caused by the fibroids (they put pressure on other organs, like bowels, bladder and kidneys) but now I discover I may have another condition which could also be contributing! Life's full of surprises ... I was particularly interested to see it mentioned somewhere that GS affects detoxification of oestrogen, as excess oestrogen is generally considered to be the cause of growth in fibroids. Suddenly everything seems to fall into place ...



An example of potential influence of UGT1A polymorphisms in altering cancer risk of individuals was preliminary demonstrated by Guillemette et al. [26] recently. In a case–control study conducted in women of African ancestry, Guillemette and colleagues observed the low activity UGT1A1 alleles to be positively associated with increased risk of invasive breast cancer. The authors suggest that the lower activity allele can lead to higher amounts of estradiol in the breast tissue, thus potentially altering the microenvironment, and increasing the risk of malignancy.


Great Sites

Action on Gilbert's Syndrome:
GIlberts Web:

List of Directories of GS Studies:
National Library of Medicine

Site for soy dangers info:

Information on SAMe: