Bilirubin protects the brain against oxidative stress

Bilirubin is commonly thought of as a toxic substance in the blood that gives children with jaundice their yellow color. But, times are a changing and now bilirubin is a powerful antioxidant. Funny how that happens. Check out the details in a blog I did on it almost 3 years ago.

Well, a new study confirms that it has strong antioxidant potential. And this holds particularly true in the brain where oxidative stress is very damaging. A small increase in oxidative stress may cause massive neuron loss in the brain.

Hemoglobin-Where much of our bilirubin comes from
Red blood cells-Where much of our bilirubin comes from

What is bilirubin?

We make bilirubin when we degrade a red protein called heme. You know heme as 1/2 of the duo that makes up hemoglobin, the protein that carries oxygen around in our blood. But heme is also in our mitochondria and elsewhere throughout the body.

When heme is freed from proteins, it is highly reactive. It’s best to get it out of there ASAP, and an enzyme called heme oxygenase is in charge of doing that. Heme oxygenase breaks heme down in to:

  • Carbon monoxide
  • Free iron
  • Biliverdin

Consequently, the enzyme biliverdin reductase rapidly converts biliverdin to bilirubin.

Oxidative stress and the brain

The brain uses a massive amount of oxygen to generate energy. Much like a car generates exhaust from burning gas, our brain generates “Exhaust” when it makes energy. One of the more damaging forms of exhaust in the brain is superoxide, a free radical.

We make most of our energy passing around electrons in our mitochondria, and one of the downsides of this is superoxide. Free radicals damage our cells by reacting with them. So it’s a tradeoff, we make energy but get free radicals in return.

Fortunately we have ways of dealing with free radicals. We make antioxidants that are very efficient at clearing them away. For example, glutathione is very good at eliminating free radicals but not for superoxide. Superoxide dismutase(SOD) clears superoxide but converts it in to another free radical.

That’s where bilirubin comes in. It has a strong affinity for superoxide and eliminates it without creating another free radical. It can also enter the mitochondria where SOD cannot. In the study referenced above, stimulating brain activity in mice that lack bilirubin increased brain damage 3x more than mice with it.

It’s quite clear that bilirubin plays a very specific role in reducing superoxide-induced oxidative stress in the brain. This likely holds true for all tissues with a high oxygen demand including the heart, liver muscle, and gut.

Of course, there is an optimal range you don’t want to exceed. Bilirubin can be toxic if too high. Normal total levels should be between 0.3-1.2mg/dL. People with Gilbert’s syndrome have slightly elevated levels(1.1-2.7 mg/dL). But, Gilbert’s syndrome is protective against heart disease so slight elevation may have benefit.


It’s clear that the the old notion of bilirubin as a toxic byproduct is wrong. On the contrary, recent evidence shows it to be a powerful antioxidant in the brain and heart. This most recent study strengthens that case and shows just how bilirubin protects us.

Wanna learn how to get some of the benefits of bilirubin? Here’s a blog showing how to increase your bilirubin levels naturally.

Study: Bilirubin Links Heme Metabolism to Neuroprotection by Scavenging Superoxide

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