Humans lost the ability to make their own vitamin C long ago, but this change may have protected our ancestors from a deadly parasitic worm infection.
The loss transformed vitamin C into something we must get from food, leaving us vulnerable to scurvy if we don’t eat enough. But in mice engineered to mimic this human trait, vitamin C deficiency blocked the worms from laying eggs, preventing organ damage, inflammation, and disease spread, researchers report December 23 in Proceedings of the National Academy of Sciences.
Schistosomes, flatworms that infect about 250 million people worldwide, live in blood vessels and produce hundreds of eggs daily. Those eggs cause the painful symptoms of schistosomiasis, including liver and spleen swelling, by triggering immune reactions as they lodge in tissues. Eggs also pass out in feces to infect snails, continuing the parasite’s life cycle.
“We hypothesized that ascorbate deficiency must confer some robust benefit to the organism in particular physiological settings that may outweigh its harms,” the researchers write.
To test this hypothesis, the team infected normal mice, which make their own vitamin C (also called ascorbate), and mice lacking the key enzyme GULO, which can’t. Without vitamin C in their diet, the mutant mice had no detectable ascorbate in their blood. Worms in these mice grew normally but absorbed no ascorbate from the host.
The result was dramatic: In vitamin C-deficient mice, the parasites produced malformed, non-viable eggs or none at all. Livers showed minimal scarring or granulomas — the immune clusters that form around eggs — compared to swollen, damaged livers in normal mice. Spleens were less enlarged, and blood tests revealed fewer eosinophils and monocytes, signs of reduced inflammation.
Even the mice’s blood cell production, disrupted by infection in normal animals, stayed closer to healthy levels without vitamin C. “Schistosome reproduction is governed by a coordinated developmental program in which contact with a male in the host stimulates female maturation and production of oocytes and vitellocytes,” the team explains, noting that vitamin C proved essential for developing the vitellocytes that nourish eggs and form their shells.
In lab dishes, adding vitamin C to female worms triggered genes for vitellocyte maturation and normal egg production. Without it, eggs were small and misshapen. The effect traced to ascorbate aiding enzymes that remove methyl groups from histones, proteins that package DNA, allowing key genes to activate.
Mice on intermittent low-vitamin C diets survived infection far better than those with steady supplies — only one in 19 died, versus more than half of normal mice. Feces from deficient mice contained no eggs, halting transmission. The team traced GULO loss across evolution, noting it happened independently in primates like us, some rodents, bats, and birds. Many parasites, including schistosomes, also lack GULO and rely on host vitamins.
“Our work explains this paradox by demonstrating a physiological benefit of vitamin C deficiency,” the researchers state.
