- Do you have a history of high bilirubin levels on blood tests?
- Do you have strange, vague & hard to diagnose gut issues with unpredictable triggers?
- Are your bowel movements irregular?
- Do you feel queasy and uncomfortable after fatty foods?
- Do yo experience ongoing anxiety & mood imbalances despite working on your health and lifestyle?
- Do you experience symptoms of oestrogen dominance & hormonal imbalances?
Many patients I meet at my naturopath clinic in Sydney present with elevated bilirubin levels on their blood test results that their GP or specialist has never discussed with them as being a potential key finding in regards to their symptoms. They’ve had mysterious gut issues for many years, many investigations with no answers, and very difficult to define symptom pictures or obvious triggers. This is a classic sign of Gilbert’s, and very frustrating for patients.
When searching ‘Gilberts Syndrome’ online, you’ll notice that it is described as a ‘benign,’ ‘harmless,’ or ‘non-serious,’ condition that doesn’t warrant treatment. Doctors are generally dismissive of the idea that it’s related to any specific symptoms that are related to a clinical picture, seeing it as innocuous.
The research would beg to differ – it is most definitely a big clue on blood testing for anyone who experiences unresolved digestive issues, anxiety & mood swings, fatigue and hormonal imbalances related to oestrogen metabolism.
Also known as familial hyperbilirubinaemia, Gilbert’s Syndrome is genetic liver condition which leads to the reduced expression and activity of enzymes which are required for the functioning of a liver detoxification pathway called Glucuronidation
Bilirubin, which is a breakdown product of heme, is meant to be detoxified via the glucuronidation pathway. People with Gilbert’s Syndrome have a 30% reduction in the activity of a group of enzymes that are responsible for detoxifying bilirubin out of the body properly. The main enzyme that is impaired which is implicated in Gilbert’s Syndrome is the UGTA1A enzyme.
This means that there is more bilirubin floating around in the bloodstream because it has not been detoxified as it should have been.
Contrary to conventional medical thought, there are great ramifications of impaired glucuronidartion and high bilirubin levels, namely because there is poor handling of Dopamine & Oestrogen, and excessive levels of bilirubin directly impact increased intestinal hyper-permeability, aka “Leaky Gut”
The glucuronidation detoxification pathway is responsible detoxification of:
- Neurotransmitters – the main ones are Dopamine & Glutamate, also serotonin.
- Hormones – the main one is Oestrogen.
- Drugs – Paracetamol, Aspirin, Non-steroidal anti-inflammatory drugs (NSAIDs), Benzodiazapenes
Gilberts syndrome patients can present with one or a combination of gut issues, psychiatric presentations and hormonal imbalances related to oestrogen metabolism. Lets take a closer look at these
Digestion & Leaky Gut in Gilberts Syndrome
Bilirubin produced in the body is eventually released into bile – a digestive liquid produced by the liver that helps your body to digest and absorb fat. Once the bilirubin is floating around the liver mixed in with bile, the liver is meant to ‘conjugate’ the biliruibin so that it can be detoxified from the body.
If you have Gilbert’s Syndrome the bilirubin is only partly conjugated, which causes the body to reabsorb the “Unconjugated Bilirubin” (UCB) due to an enzyme called Beta-glucuronidase. This means the bilirubin is ‘retoxified’ back into circulation, leading to the high bilirubin levels seen in Gilbert’s Syndrome
The higher levels of UCB floating around the gut can have a range of potential effects:
- Loose stools, watery diarrhoea
- Increases paracellular permeability by disrupting tight junctions of the gut wall, i.e. it directly drives leaky-gut
- Upper GIT discomfort – reflux, heartburn, ‘queasiness’ or nausea after eating
- Delayed gastric emptying – a feeling of foods ‘just sitting there in my stomach like a brick’
- Abdominal pain & cramping
- Difficulty digesting fatty foods and high-protein meals
- Increased risk of developing gallstones
Due to the direct effects of high bilirubin on gut-wall permeability, it is common to see dysbiosis – imbalance of ‘good’ and ‘bad’ gut bacteria – when assessing gut microbiome testing on patients with Gilbert’s Syndrome
Small Intestinal Bacterial Overgrowth (SIBO) is also very common in Gilbert’s, as the small intestine is that part of the gut where leaky-gut develops. Supporting glucuronidation is essential in these patients to ensure their gut dysbiosis or SIBO does not relapse.
Nervous System & Brain Health
Is UCB an underestimated neurotoxin? Research is continuing to highlight that this is very likely for a number of reasons
- Higher levels of UCB are sometimes observed in newborns, and as children they have a significant increase in developing a mental health disorder
- There is some evidence regarding UCB’s role in the schizophrenia – existing studies have observed a 20% prevalence of Gilbert’s Syndrome in schizophrenic patients, although other studies have been conflicting to be able to associate Gilbert’s Syndrome with a full-spectrum diagnosis of schizophrenia.
- However there are numerous studies which observe a higher rate of excess UCB levels found in patients who experience acute, remitting psychosis. Schizophrenia & psychosis are characterised by dopaminergic dysregulation
- UCB insults glial cells – our immune cells of the central nervous system. This leads to dysregulation of glutamate metabolism – an excitatory neurotransmitter that can drive anxiety, impaired cognition, excitable behaviours, aggression and is involved with the neuropathology of schizophrenia
- The insult to glial cells leads to the release of excessive pro-inflammatory chemicals that impact learning and memory
Impaired dopamine handling, glutamate dysregulation & inflammatory cytokine production that are influenced by high levels of UCB can have a dramatic impact on mental health and can be related to patients experiencing anxiety, fatigue & cognitive impairment. In some individuals it can even be related to more extreme events such as acute, remitting episodes of psychosis
Hormonal Imbalances – Oestrogen Dominance
Oestrogen dominant symptoms & conditions are extremely common in Gilbert’s Syndrome due to inadequate detoxification of oestrogen via the glucuronidation pathway:
- Heavy and/or painful periods
- PMS – anxiety, fatigue, headaches, migraines, bloating
- Low libido
- Weight gain
Post-menopausal women may also be at a slight increased risk of developing breast-cancer
I have written at length about oestrogen metabolism issues in relation to copper toxicity and histamine intolerance. They are both tied to poor digestive function, gut dysbiosis & leaky gut (everything is connected).
Men with Gilbert’s syndrome regularly present with symptoms of low testosterone and issues with oestrogen metabolism:
- Low libido
- Erectile dysfunction
- Mood swings
- Hair Loss
- Loss of muscle mass
- Increased body fat
Testing & Diagnosis
High Total Bilirubin (“Unconjugated Bilirubin”) across repeated blood tests is the biggest clue for Gilberts Syndrome – anyone with a consistent pattern of >15 ummol/L, not just a one off elevation.
You can get a clearer idea on whether or not it’s true Gilbert’s Syndrome by testing separately for Direct Bilirubin, also known as “Conjugated Bilirubin.” This is the bilirubin that has gone through glucuronidation, which will appear within the normal range in Gilberts’ Syndrome patients.
The Royal College of Pathologists of Australia (RCPA) criteria is to test for both Total and Direct bilirubin. If diagnosis is uncertain they recommend a fasting blood test alongside a non-fasting test, where the fasting test should exceed the non-fasting level by >50%.
In reality, GPs will rarely bother with testing beyond the Total Bilirubin. It is usually obvious enough from routine blood testing where Total Bilirubin is persistently >15 ummol/L that a patient has a compromised glucuronidation detoxification pathway
UGT A1A Enzyme testing is also available to confirm if it may be true Gilbert’s Syndrome, but the persistent high bilirubin levels combined with symptoms presentation is enough to just get on with treatment which is quite simple.
If other more serious reasons for high bilirubin have been excluded – haemolytic anaemia, hepatitis, cirrhosis, blocked bile ducts due to gallstones – then Gilberts Syndrome is likely to be the correct diagnosis.
Gilbert’s Syndrome treatment should be multi-layered and focused around supporting the glucuronidation detoxification pathway, digestive function, gut microbiome, leaky gut and dietary & lifestyle strategies. Please consult with your doctor before ceasing any medications.
The following compounds & dietary factors directly slow down UGT enzyme function & increase bilirubin levels
- Oestrogen – Oral Contraceptive Pill (OCP), Hormone Replacement Therapy (HRT)
- Retinoids (Vitamin A) – Vitamin A supplements inhibit the UGT enzyme, so high-doses are not recommended. Interestingly, the medication acne Roaccutane reduces liver toxicity and normalises bilirubin levels in Gilbert’s Syndrome patients.
- Medications – NSAIDs (e.g. Ibuprofen), paracetamol, oral contraceptive pill (oestrogen), many antidepressants, steroids, opiates, testosterone replacement therapy
- Fasting – is not recommended for Gilbert’s Syndrome because it reduces UGT enzyme activity and reduces bilirubin clearance. Breakfast is the most important meal because this is when our gut motility and gastric emptying is fastest.
- Low fat diets – absence of dietary fat increases bilirubin levels. Ensure meals contain adequate amounts of beneficial oils
Stress & Exercise
Stress directly increases bilirubin levels, as does vigorous exercise. Stress management, HPA Axis support & balancing out physical exercise with restorative practises (breathwork, yoga etc.) are all highly beneficial for Gilbert’s Syndrome.
Supplements To Support Glucuronidation – Discuss With Your Practitioner
- Broccoli Sprout (Sulforaphane)
- Magnesium + B-Vitamins
- Herbal medicines – bile-stimulating & bitter herbal medicines help increase bile flow, reduce gallbladder stagnation and increase overall bilirubin output
Microbiome & Leaky-Gut Support
- Fibre & Prebiotics – help to reduce bacterial species in the gut that produce beta-glucuronidase, speed up transit time and stimulate the growth of beneficial gut bacteria that reduce bilirubin
- Intestinal Permeability support -Probiotics, Quercetin, Glutamine, Vitamin D, Anti-inflammatory herbal medicines, EPA/DHA (Omega-3), Zinc Carnosine can all be helpful here
Benefits Of Gilbert’s Syndrome? Living Longer!
Discovering you have Gilbert’s Syndrome is not all bad news – bilirubin is a major antioxidant that appears to protect DNA from damage, lengthening telomeres and having a strong anti-ageing effect.
It is protective many ways – Gilbert’s Syndrome patients have lower rates of cardiovascular disease, better glycemic control in diabetes, reduced mortality in hereditary haemochromatosis, lung cancer and colon cancer.
Just make sure you are supporting the glucuronidation pathway & gut health to ensure you don’t experience the symptoms of high UCB levels!