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Vitamin C Deficiency Linked to New Health Risks - 2002-05-01

Researchers have discovered the first health problems caused by vitamin C deficiency since it was linked to scurvy in the 18th century. The findings could have implications for preventing stroke and complications related to premature birth.

European sailors in the age of tall ships learned that to maintain healthy muscles, stave off internal bleeding, keep their teeth, and prevent other symptoms of scurvy on long voyages, they should eat fresh fruits and vegetables. These are foods rich in vitamin C, which plays a role in the manufacture of a protein called collagen, that gives shape to connective tissues and strength to skin and blood vessels.

Preventing scurvy is vitamin C's only proven function. But mice experiments at the U.S. government's National Institutes of Health show that a deficiency in this nutrient leads to two other serious conditions. The lead researcher, physician Robert Nussbaum, explains "those mice died very, very soon after birth with many of the complications that we usually associate with premature birth in humans - a particular pattern of bleeding in the brain and also failure of normal function of the lung."

Dr. Nussbaum's team reports in the May issue of the journal Nature Medicine that they used mice specially bred to lack one of two molecules that transport vitamin C into the cells of the body. Therefore, the animals' tissues were starved of the nutrient.

Could the resulting brain bleeding and lung malformation be related to scurvy? Does poor collagen formation underlie them?

Dr. Nussbaum thinks not - at least not for the brain bleeding - because the animals did not bleed anywhere else and their skin was unaffected, unlike sailors of old. Instead, he thinks the mice brains sensed an oxygen deficiency and overreacted, not because they actually lacked oxygen, but because vitamin C is necessary for the chemical reaction that senses the oxygen level.

"So what we think may be happening in the brain of these newborn mice is that you get dilation of the blood vessels," said Dr. Nussbaum, "the blood vessels expand enormously in an attempt to improve oxygen delivery to the brain, and it's that dilation of the blood vessels that causes them to rupture."

However, the researchers cannot explain the lung problems in the vitamin C deficient mice. Determining this is the next step in their research.

The scientist who helped discover the molecules that transport vitamin C into tissues, Mattias Hediger at Brigham and Women's Hospital in Boston, gives the National Institutes of Health group high marks for their findings.

"This new paper reveals the importance of the vitamin C transporters they have removed. These investigators really found new roles for vitamin C beyond those we know from findings of the disease scurvy," he said.

Mr. Hediger says the findings suggest that vitamin C might be useful in protecting against the sort of damage involved in stroke, where blood vessels rupture in the brain like they did in the newborn mice.

"It definitely looks like vitamin C is required for stroke prevention just before birth, and actually it has been known before that relatively high concentrations of vitamin C are accumulated in the fetal brain. It's however quite possible that accumulation of higher levels of vitamin C could prevent against stroke in the adult," noted Mr. Hediger.

But Dr. Nussbaum sees the most value in his work for understanding problems related to premature birth. He reminds us that humans and other primates cannot make vitamin C, so the fetus depends on what its mother consumes. His study implies that vitamin C deficiency in the mother, late in her pregnancy, may play a role in the complications of prematurity.

"I wanted to raise the issue that people who deal with premature infants should think about vitamin C as perhaps an important constituent of this entire process," he said.