Why addressing Gilbert's Syndrome Matters for Better Mental Health

Gilbert syndrome is often dismissed as a benign genetic quirk — a mildly elevated bilirubin level noted on a routine blood test, with doctors typically reassuring patients that "it's nothing to worry about." But if you're someone who struggles with fatigue, brain fog, mood swings, anxiety, or depression, Gilbert syndrome may deserve far more attention than it usually receives.

In this article, I want to explore two crucial reasons why Gilbert syndrome should be taken seriously from a mental health perspective, and share a practical protocol you can implement to support your body.

1. Energy and Mental Health Are Deeply Connected

Dr. Christopher Palmer, a Harvard psychiatrist and author of the groundbreaking book Brain Energy, has put forward a paradigm-shifting hypothesis: mental disorders are, at their core, metabolic disorders of the brain. In his framework, anything that disrupts cellular energy production — particularly mitochondrial function — can manifest as symptoms we typically label as psychiatric: depression, anxiety, bipolar disorder, schizophrenia, ADHD, and more.

This is a profound reframing. It means that fatigue is not just an unpleasant side effect of poor mental health — it may actually be a driver of it. When your cells cannot produce energy efficiently, your brain, which consumes roughly 20% of your body's energy, suffers first.

People with Gilbert syndrome frequently report low energy, exercise intolerance, and post-exertional fatigue. When bilirubin rises (during fasting, dehydration, illness, or intense endurance exercise), many describe worsening mood, irritability, brain fog, and low motivation. Through the lens of Brain Energy theory, this is not a coincidence — it's a metabolic signal that deserves attention.

2. Gilbert Syndrome Impairs Detoxification via UGT1A1

Gilbert syndrome is caused by a reduced activity of the enzyme UGT1A1 (UDP-glucuronosyltransferase 1A1). This enzyme is best known for conjugating bilirubin so it can be excreted — which is why people with Gilbert syndrome have higher circulating bilirubin.

But UGT1A1 does much more than process bilirubin. It's a key player in Phase II liver detoxification responsible for glucuronidating (neutralizing and preparing for excretion) a wide range of environmental toxins, hormones, and drugs.

This means people with Gilbert syndrome may have a reduced capacity to clear certain pollutants that we're all exposed to daily. Over time, this can contribute to a higher toxic load, oxidative stress, mitochondrial dysfunction — and, coming full circle, worsened brain energy and mental health.

Some of the key pollutants processed by UGT1A1 include:

- Benzo[a]pyrene (BaP) metabolites — found in tobacco smoke, grilled/charred meat, diesel exhaust, and air pollution

- Polycyclic Aromatic Hydrocarbons (PAHs) — from wood/charcoal smoke, exhaust fumes, and roasted coffee

- Bisphenol A (BPA) — plastic bottles, food can linings, thermal receipts

- Phthalates (e.g., DEHP metabolites) — plastics, cosmetics, perfumes

- Parabens — cosmetics, shampoos, lotions

- Acrylamide — starchy cooked foods like fries, toasted bread, and coffee

For someone with reduced UGT1A1 activity, minimizing exposure to these compounds is not just good hygiene — it's a strategic move to protect brain energy and mental well-being.

A Practical Protocol for Gilbert Syndrome

Here is a synthesis of evidence-based lifestyle recommendations, drawing on the systematic review by Goluch et al. (2024) published in Nutrients [1]:

Diet and Hydration

- Consume kombucha regularly — it contains gluconic acid, which supports glucuronidation pathways

- Increase citrus fruits (lemons, oranges, grapefruit) which support UGT1A1 activity

- Eat more cruciferous vegetables — cabbage, turnip, radish, arugula, watercress

- Include apiaceous vegetables— carrot, celery, parsley, coriander

- Stay well hydrated, especially during exercise or heat waves — an isotonic drink or water with a splash of orange juice works well

Lifestyle

- Avoid prolonged fasting — fasting can significantly raise bilirubin and worsen symptoms

- Avoid endurance sports — long-duration, high-intensity exercise can trigger flares. Favor shorter, moderate-intensity movement instead

Toxin Vigilance

Given UGT1A1's role in detoxification, be especially mindful about limiting exposure to the pollutants listed above (BaP, PAHs, BPA, phthalates, parabens, acrylamide). If you suspect a high toxic load, consider testing for chemical pollutants through a functional medicine lab.

Targeted Supplementation

For a curated list of supplements that support UGT1A1 activity, mitochondrial function, and detoxification pathways in Gilbert syndrome, you can consult my recommended protocol here:

👉 [Supplement Protocol on SimplyCure](https://app.simplycure.com/store/fabien-villotte/protocols/c0a1065b-2130-4e3a-862d-d5d26fa0eafc)

Final Thoughts

If you have Gilbert syndrome and also struggle with mood, anxiety, or unexplained fatigue, don't accept the standard "it's benign, ignore it" narrative. Your genetics are giving you valuable information: your body may need extra support to produce energy and to clear environmental toxins. Addressing both fronts — through diet, lifestyle, targeted supplementation, and toxin avoidance — can be a genuine turning point for your mental health.

Your brain runs on energy. Protect it accordingly.

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Reference:

[1] Goluch Z, Wierzbicka-Rucińska A, Książek E. Nutrition in Gilbert's Syndrome — A Systematic Review of Clinical Trials According to the PRISMA Statement.Nutrients. 2024 Jul 12;16(14):2247. doi: 10.3390/nu16142247. PMID: 39064690; PMCID: PMC11280271.