Most mammals produce their own vitamin C using an enzyme called GULO. Around 60 million years ago, humans lost this ability, which scientists long viewed as evolutionarily neutral since vitamin C from diet compensated for the loss. But new research suggests that the deprivation of this essential molecule was not an innocuous evolutionary shift but actually a clever defense against parasitic infections.
“One of the reasons that we lost this metabolic gene, which makes an essential molecule that turned this into a vitamin, is that metabolically our bodies are adapted to work to deal with infections, including parasite infections,” Michalis Agathocleous at the University of Texas Southwestern Medical Center told New Atlas. “There is a very strong benefit to vitamin C deficiency in an animal that’s infected with parasites.”
Agathocleous and his colleagues had been studying vitamin C for years, intrigued by its role in blood-forming stem cells. The evolutionary tree indicates ascorbate (vitamin C for us) production is an ancient trait shared by most life forms, but it has been lost multiple times. The team observed that even parasites lost vitamin C synthesis over the course of evolution.
Agathocleous believed that because parasites rely on their hosts for nutrients, they might need to obtain vitamin C from them. Another clue came from a study that found adding vitamin C to parasitic schistosome worms in lab dishes enabled them to lay eggs. This suggests a possibility that parasitic worms might be harvesting vitamin C from its host, and therefore, vitamin C deficiency in a host organism could help protect from those parasites.
To test this hypothesis, the team bioengineered mice without the GULO enzyme to mimic humans’ vitamin C dependency. They infected the mice with Schistosoma mansoni, commonly known as blood flukes, along with normal ascorbate-producing mice. The GULO-deficient mice were fed diets low in vitamin C.
Researchers observed that normal mice developed swollen livers and spleens, along with severe inflammation driven by parasite eggs. Meanwhile, the vitamin C-deficient mice were protected: parasites grew normally, but females couldn’t produce mature eggs, preventing both disease transmission through feces and most infection-related deaths.
“If the animal can make its own vitamin C, the vitamin C levels are always high, and the schistosome lays eggs constantly. But if the animals are deficient in vitamin C, because they cannot synthesize it, then there’s quite strong protection,” says Agathocleous.
But what about scurvy, a fatal disease caused by vitamin C deficiency? Agathocleous told us that it takes several months of deprivation from vitamin C to develop the symptoms of scurvy. Parasites like schistosomes, on the other hand, operate on a much quicker timeline.
“We think there is an acute benefit provided by the fact that the parasite is working on a faster time scale than the human or the animal host,” he told us.
The new study was published in Proceedings of the National Academy of Sciences.
