Gilbert's Syndrome

Dr. Damien Downing's Column

...expert advice on treating environmental illnesses with ecological and nutritional medicine.

Dr. Damien Downing M.D. is President of the British Society for Ecological Medicine (www.ecomed.org.uk), Chief Medical Advisor to the charity Yes to Life (www.yestolife.org.uk), and Editorial Board member of the Orthomolecular News Service (www.orthomolecular.org). He is a practitioner of ecological medicine in London (www.newmedicinegroup.com) and York (www.naltd.co.uk) and author of several books including The Vitamin Cure for Allergies (USA, Basic Health Books, 2010).

You can benefit from Dr. Downing's wisdom and experience by visiting us at The Environmental Illness Resource regularly to read articles from his newsletter!

Thursday, May 12th, 2011:

Gilbert's SyndromeGilbert's Syndrome

by Damien Downing MD

Gilbert’s Syndrome is a genetic impairment in the glucuronidation pathway in the liver. This is one of the 4 components of the Phase 2 Detoxification System, also known as Hepatic Microsomal Enzymes. (Phase 1 is the Cytochrome P450 System, which is also subject to genetic variations.) Gilbert’s is the only recognised common inherited disorder of Phase 2; in fact 50% of people have genetic variations of the glutahione S-transferase enzymes, which can have major health consequences. Estimates of the prevalence of Gilbert’s range from 2% to >5% of the population.

Although it has often been said to have no clinical significance, this does not explain why Gilbert’s “sufferers” are relatively common among our patients. It is likely that such people are more vulnerable to adverse effects of physical, particularly hepatotoxic, stress. Indeed, stress tests have been used to confirm the diagnosis (calorie restriction to 400/day; intravenous nicotinic acid; oral Rifampicin); all these raise the bilirubin by competing for the role of substrate to the limited enzyme. Those with Gilbert’s do seem to exhibit symptoms more often than is the norm after infections, toxic exposures and the like. It is probable that they are more vulnerable to, for instance, the potentially severe consequences of paracetamol toxicity.

Glucuronidation detoxifies all of the following molecules:

Endogenous:

Steroid hormones
(endogenous and exogenous)
Oestrogens
Melatonin
Bilirubin

Medications:

Salicylates
Opiates
Benzodiazepines
Paracetamol
Propranolol
Valproate
Digoxin

Chemicals:

Carbamates
Phenols
Anilines

Treatment options

There are no known pharmacological agents that benefit the condition.
Cruciferous vegetables, particularly Brussels sprouts, appear to stimulate the enzyme (but will also stimulate the CYP1A2 sub-enzyme of Phase I detox, so this may be a two-edged sword).
Reducing exposure to other chemicals (see list above) processed by this route will reduce competition for the limited enzyme availability (but will also increase metabolism of hormones, which may be good or bad).
Relevant nutrients (L-glutamine, aspartic acid, niacin, vitamin B6, Fe, Mg) may support the enzyme, but nobody has yet demonstrated that this works.
General support of the hepatic detox pathways will certainly do no harm, and may benefit by increasing the parallel pathways of detoxification.