Yellow pigments that cause jaundice may shield malaria

During jaundice, the same yellow pigment can make the skin sick and can actually save lives by protecting people from the deadliest effects of malaria.

New research published in science shows that bilirubin (seemed as cellular waste) is like an internal bodyguard, opposing parasites that kill 600,000 people a year. This finding tilts conventional medical thinking, suggesting that what appears to be harmful on the surface may be the evolutionary clever defense mechanism.

Scientists at Johns Hopkins Medicine and the Gulbengki Institute in Portugal discovered this protective effect by studying blood samples from 42 malaria patients in Gabon, Africa. Asymptomatic infections have ten times more unprocessed bilirubin in the blood than people with severe symptoms.

Jaundice paradox

According to research in medical journals, jaundice affects 2.5% to 50% of patients with malaria. For decades, doctors have viewed this yellowing as another disturbing symptom. But the research team suspected something different was happening.

“Bilirubin was once considered a waste product,” explained Bindu Paul, associate professor of pharmacology at Johns Hopkins. “This study confirms that this could be a key protective measure for infectious and potentially neurodegenerative diseases.”

Scientists tested their theory using mice designed to lack BVRA, an essential protein for bilirubin production. When exposed to rodent malaria, these mice died while surviving normal mice.

How to fight back bilirubin

The study found a multi-pronged attack on malaria parasites by bilirubin. This lipophilic molecule slides within infected red blood cells and targets the power center of the parasite, namely the mitochondria. It can be considered as a computer network that is stuck in a virus.

But bilirubin is more than that. The study shows that it also destroys blood cell crystals, a process parasite used to detoxify the iron-rich environment in red blood cells. Without this detoxification system, parasites are essentially poisoned with their own waste.

The most notable is the attack on the food supply of the parasites by bilirubin. It damages what researchers call “food vacuoles” (actually the stomach of the parasite), thus preventing it from obtaining the amino acids needed to survive and reproduce.

Key research results:

• Asymptomatic malaria patients have 10 times more unprocessed bilirubin than symptomatic patients
• Mice lacking bilirubin production die from malaria, while normal mice survive
• Bilirubin destroys parasite mitochondria, blood tuple and nutritional learning
• Higher bilirubin dose restores survival in genetically modified mice

Evolutionary trade-offs

This finding suggests that jaundice in malaria represents what scientists call an evolutionary trade-off. Malaria – Populations in endemic areas may have developed tolerate bilirubin levels as protection against the disease. However, this same mechanism increases the risk of neonatal jaundice, which may damage the developing brain.

Ana Figueiredo, a doctoral student who led the study, believes that the findings go beyond malaria. The study shows that bilirubin may prevent other infectious diseases, opening up new avenues of treatment.

Will this lead to new treatments? Paul and her colleagues are exploring whether drugs that increase bilirubin production or delivery can prevent the worst effects of malaria. Given that malaria affects more than 260 million people per year in tropical regions, this treatment can save countless lives.

Beyond malaria

The study, based on Paul’s early work, showed that bilirubin protects brain cells from oxidative damage. This connection between ancient defenses against infection and modern neurodegenerative diseases emphasizes how evolutionary solutions often have multiple purposes.

Paul plans other studies to understand the brain protective effects of bilirubin. As researchers continue to uncover the true purpose of “waste products,” it seems clear: evolution rarely produces useless by-products. Sometimes something that looks like biotrash is a treasure.

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