The Superman Disorder?

When I was 13 years old I was diagnosed with Gilbert's Syndrome, a genetic disorder affecting the promoter of a gene for the enzyme glucuronyltransferase, which conjugates bilirubin. 5-10% of the population have GS, and it is benign, leading only to elevated levels of unconjugated bilirubin in blood tests and occasional slight jaundice, which friends of mine have sometimes remarked on.

What seems weird, though, is that in the last few years there has been a raft of statistical epidemiological studies suggesting that us GS guys have a huge, invisible health shield! Those of us with the disorder appear to be  protected, sometimes strongly,  against cancer, cardiovascular disease, respiratory disease and kidney disease, and have lower BMIs, reduced cholesterol, more elastic arteries, reduced inflammation status and all sorts of other yummy stuff. There was even an article published last year showing success in the bottom line: in a study of 25,000 people over 350,000 person-years the overall mortality  of us Gilbert's Grenadiers was only half that of normal people.

Why would this be? The suggestion (albeit disputed) is that protection arises at least in part because unconjugated bilirubin is a powerful antioxidant, and therefore protects against oxidative stress. That would then be a bit like having had your ration of five fruits and vegetables before you even get up in the morning.

I'm not buying it, of course. There has to be a catch somewhere, doesn't there? Hyperbilirubinemia in infants can lead to irreversible kernicterus, or brain damage. Also, drug toxicity would appear to be worse in some cases for us guys. So I'm waiting for the negative metabolic effects of GS to be elucidated using systems medicine approaches. But until that time, I'm formally in the superman club!