sydney naturopath

Got High Bilirubin? Get A Load Of Gilberts Syndrome – A Gut-Brain Phenomenon

  • 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
  • Carcinogens

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
  • Fibroids
  • Endometriosis
  • 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
  • Fatigue
  • 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.

Treatment Strategies

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

  • Alcohol
  • 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

  • Calcium-D-Glucurate
  • Broccoli Sprout (Sulforaphane)
  • Zinc
  • SAMe
  • 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!

24 replies
  1. Kate Thirkell
    Kate Thirkell says:

    I live in Uk I have Gilbert’s and have found this so helpful thank you!
    I currently take a low dose of oestrogen and Androfeme testosterone to help with my peri menopause symptoms which has helped relieve some of them. But should HRT be avoided given how I will detoxify it. Any advice on this would be welcome, thank you.

  2. Mel
    Mel says:

    So glad I found this blog its been so helpful!
    For so long I’ve pretty much been feeling like something is wrong constantly fatigued and just off and every time I have done a blood test it has come back fine, but every time my doctor mentions looks like you have “Gilberts syndrome” but it doesn’t have any effects so don’t worry about it….

    Then to find this and see it actually can cause some symptoms I’m experiencing!

    Thank you for sharing!

  3. Rud
    Rud says:

    Whenever the weather starts to get warmer (April, May) I all of a sudden stop feeling hungry. Im normally a good eater, and I can barely get myself to eat half of what I usually do.

    As a result I lose a lot of weight over the course of a summer, and when tested, I have high levels of unconjugated bilirubin.

    What’s more strange is that towards autumn, these symptoms go away and I start to eat well and regain the weight I lost, and the levels of bilirubin decrease. This is happening for some years now.

    I started feeling these same symptoms last May and was tested for virtually everything, with nothing coming up besides a very high level of bilirubin, to the extent that my eyes are yellowish.

    It is the end of April now and my symptoms have persisted! We have tried everything to try to see what causes this but we are left with no answers, and the issue remains unresolved. Please, what can I do to make this go away.

    I am active and my health was excellent before all of this, and I just want to stop experiences these gastric symptoms.

    Any advice will help.

    • Steven Judge, Clinical Naturopath Sydney
      Steven Judge, Clinical Naturopath Sydney says:

      Hi Rud,

      You can get started with some of the basic supplements that support the glucuronidation pathway (calcium-d-glucurate + broccoli sprout), although it’s always best to work. with a practitioner to ensure individualised treatment.

      I work online with client internationally- please get in touch if you’d like to make a booking

  4. Kate
    Kate says:

    Thanks for the post.
    I’m pretty sure I’m about to be diagnosed with Gilbert’s after years of symptoms and being ignored by doctors and it was good to see a functional medicine perspective.

    In my most recent blood tests as well as high bilirubin I also had high ALT and low ALP (pretty consistently). I’ve had an ultrasound to rule out any liver damage and it’s not hepatitis either. You mentioned other liver enzymes in the post- could the high ALT be down to Gilbert’s? What about low ALP (perhaps just lack of magnesium/ zinc, which I’m working on).

  5. steve fishman
    steve fishman says:

    I have GS. I know there is a cardiovascular benefit, but how much so? Does GS negate high cholesterol? Has there been any studies that you know of? Would that mean the some with GS could avoid taking a statin (which might make them jaundiced). Thanks

  6. Michal
    Michal says:

    Hello, I have inherited high bilirubin levels and histamine intolerance since childhood. My symptoms are getting crazy and no doctor could help me. The worst symptoms are daily brain fogs and cognitive imbalances. Does Histamine intolerance affect bilirubin levels? Is there any help to make me feel like a human again and not a walking zombie?

    • Steven Judge, Clinical Naturopath Sydney
      Steven Judge, Clinical Naturopath Sydney says:

      Hi Michal,

      A link between gilbert’s and histamine intolerance is likely to be that the glucuronidation pathway is responsible for detoxifying oestrogen. If it is compromised (as it is in Gilbert’s Syndrome), then a build up of oestrogen will worsen the histamine intolerance (read my other blog on histamine intolerance.

      Improving oestrogen detoxification via the liver and the bowels would be a treatment priority

  7. Pascale
    Pascale says:

    Hello Steven, I have GS and cholesterol levels which keep on growing. I wonder what the effect of GS is on the ever growing LDL. Do you know of any studies? Thanks Pascale

    • Steven Judge, Clinical Naturopath Sydney
      Steven Judge, Clinical Naturopath Sydney says:

      Hi Pascale,

      I’m not aware of any negative links with GS and cholesterol levels. Bilirubin is in-fact an antioxidant that has been shown to suppress the oxidation of LDL, and it is anti-inflammatory.

      For cholesterol issues I’d look more into excess sugar and carbohydrates relative to a lack of protein & EPA/DHA (omega-3), alcohol, smoking, heated vegetable oils and stress.

      LDL testing on it’s own is not an accurate marker of atherosclerosis risk – a more comprehensive panel of LDL subtractions, and/or a coronary calcium scan will give you more accurate insights

  8. Paige Sanders
    Paige Sanders says:

    Thank you for the really informative post!

    I am wondering if you know what antidepressants slow down UGT enzyme function & increase bilirubin levels?

  9. Nick
    Nick says:

    Hi, I have been diagnosed with GS for over 30 years. Every 5/6 years I have a really bad bout of stress induced IBS and stools are always soft and yellow in colour. I have all sorts of investigations but Is it possible that this might be down to GIlbert’s ?

  10. Brian Malaney
    Brian Malaney says:

    Thanks for the research. One point that I could use clarification on: you say low fat diets aren’t good for keeping bilirubin low but high fat foods definitely are a trigger for stomach distress for me. Is there a distinction you can make on the conflict there? Or things you have seen on how to get enough fats without triggering symptoms?

    Thanks again.

    • Steven Judge, Clinical Naturopath Sydney
      Steven Judge, Clinical Naturopath Sydney says:

      Hi Brian,

      While dietary fat from optimal sources e.g. avo, olive oil, butter, other sources of dairy if not intolerant (yoghurt, cheese), animal proteins etc. are important to get in, if there are obvious symptoms from ingesting even a small amount of fat then there may be some underlying issues with pancreatic digestive function (e.g. lipase needed to breakdown fats). This could also be an underlying symptom of Small Intestinal Bacterial Overgrowth (SIBO), if so this would need to be treated. It can also be a symptom of poor digestive enyme production due to nervous system dysregulation from stress and/or nutrient deficiencies.

      Essentially you’d need to address the underlying cause/s of why you can’t digest fat, which could be multifactorial. Digestive enzymes can be nice temporary support when eating meals while figuring these out.


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