Have You Heard Of Gilbert’s Syndrome?
Gilberts syndrome is a genetic condition in which the body is unable to effectively clear bilirubin from the body (unconjugated hyperbilirubinemia) which results in impaired detoxification. It is arguably the most common syndrome known to humans! Bilirubin is the product of broken down red blood cells in the body, a natural and consistently occurring process. The mechanism which clears bilirubin from the body is called glucuronidation, a phase II liver detoxification pathway. In Gilberts Syndrome, this glucuronidation pathway is compromised, leading to high bilirubin levels and the overwhelm of this pathway – reducing its other vital functions, such as the breakdown of common medications such as paracetamol. According to a 2012 study, Gilberts Syndrome should be considered a potential risk factor toward drug toxicity.
Understanding Gilbert’s Syndrome
Bilirubin is produced when red blood cells are broken down and removed from the body via a mechanism called glucuronidation within the livers phase II detoxification pathway. Glucuronidation converts unconjugated bilirubin to conjugated bilirubin, a water-soluble form which is easily excreted from the body. In Gilbert’s syndrome, the liver enzyme- bilirubin UDP-glucuronosyltransferase (UGT) that performs this reaction is impaired, leaving the liver unable to keep up with the demands of this conversion. As a result, unconjugated bilirubin levels begin to rise. Whilst bilirubin has beneficial antioxidant properties, elevated levels of unconjugated bilirubin can have harmful pro-oxidant effects as well.
- If levels rise too high they can cause jaundice, which is a yellowing of the skin and whites of the eyes.
- upper abdominal pain
- fat intolerance
- loss of appetite
- brain fog
WHAT TO BE MINDFUL OF IN GILBERTS SYNDROME!
- Fasting is not ideal for those with the syndrome as the enzyme bilirubin-UGT reduces in fasting states, further elevating bilirubin.
- Typically, bilirubin rises when the body is under stress, such as in times of dehydration, illness, vigorous exercise or during menstruation.
- Drugs whose elimination is impaired in those with Gilberts Syndrome include; irinotecan, paracetamol, morphine, oxazepam, temazepam, amitryptiline, ritodrine, diflunisal and zidovudine.
- Gilberts Syndrome can implicate the detoxification of exogenous compounds which also rely on glucuronidation; including hormones such as estrogen. This suggests that Gilbert Syndrome may contribute to conditions in which high estrogen is implicated.
- The presence of Gilberts Syndrome as a contributory factor to other conditions including: newborn jaundice, thalassemia, spherocytosis and Crigler-Najjar syndrome (another genetic unconjugated hyperbilirubin condition).
- Gilberts Syndrome can affect dopamine levels and therefore contribute to mental health disorders.
- A relationship has been observed between Gilberts Syndrome and schizophrenia.
Treatment that supports phase II detoxification has the potential to counteract the disruption caused by unconjugated bilirubin. Avoiding alcohol, fasting and drug use (as listed above where possible) will avoid unnessasarily elevating bilirubin. Supportive supplementation such as N acetyl cysteine, calcium D glucarate and the cruciferous vegetables can be useful. If liver disease is also present then supplementation with SAMe (S-adenosylmethionine) may also be useful.
- Oxford Academy- Gilberts Syndrome
- NCBI-Gilbert syndrome redefined
- NCBI-Heterogeneity of paracetamol metabolism
- Oxford Academy-mutation in the gene
- Wiley online library-Molecular genetic basis of Gilbert’s syndrome
- ADA-Reduced Caloric Intake
- NEJM-Relation between Caloric Intake
- NCBI-Bilirubin inhibits transport of neurotransmitters in synaptic vesicles