Vitamin C deficiency linked to cerebral bleeding

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A study of mice has shown a link between a lack of vitamin C during
pregnancy and cerebral bleeding which can occur after premature

A study of mice has shown a link between a lack of vitamin C during pregnancy and cerebral bleeding which can occur after premature birth.

Scientists at the National Human Genome Research Institute (NHGRI) in the US demonstrated that mice deprived of vitamin C during pregnancy and birth died almost immediately after birth from bleeding in the brain and respiratory failure.

In humans, intracerebral haemorrhage, lung complications and respiratory failure are frequent causes of serious morbidity and death in premature infants. Maturation of the lungs occurs during the final few months of human gestation. A child born before this maturation is at high risk for these complications in the immediate postnatal period.

"What I'm suggesting is that we need to take a look at whether vitamin C in human foetuses before birth, transported from the maternal circulation, is a normal physiological factor that helps to mature and protect the lungs and brain of newborn infants,"​ said Dr Robert Nussbaum, chief of the Genetic Disease Research Branch at NHGRI and co-author of the paper.

"There may be a link between sub-clinical deficiencies invitamin C in the mother - that is, a deficiency notsignificant enough to cause scurvy - and the problems thatcan occur when the foetus prepares to leave the womb. Wedon't know for sure. What I'm suggesting is that the workin mice points to an area that needs to be investigated."

In the study, scientists created a mouse with a defective 'Slc23a1' gene, which encodes the transporter protein that gets vitamin C intocells. They discovered that this so-called 'knockout' model could notdeliver vitamin C (ascorbic acid) from the blood to manyfoetal tissues nor transport it across the placental border.Hence, the 'Slc23a1' gene-deficient mice had markedlyreduced levels of ascorbic acid in their blood and very lowor undetectable levels in their brains and other organs.

What surprised scientists was the discovery that thevitamin C-deprived mice died within minutes after birth dueto massive cerebral haemorrhage andcomplete respiratory failure when their lungs failed toexpand. These severe health problems occurred whether thenewborn mice were delivered normally after 21 daysgestation, or delivered early at 18.5 to 19.5 days byCaesarian section to avoid birth trauma.

Also, the abnormalities in lung function could not beexplained by loss of surfactant protein production, sincelevels of a critical protein, surfactant B, were normal.Intracerebral haemorrhage due to vascular fragility, ora defect in collagen processing from low vitamin C levels - similar to the effects of scurvy - were ruled out since4-hydoxyproline levels also were normal. The mice haddeveloped normally while in the womb, including normalweight gain.

"One could come back to the power of the knockout mouse,"​said Dr. Mark Levine, chief of the Molecular and ClinicalNutrition Section at the National Institute of Diabetes andDigestive and Kidney Diseases and senior staff physician atthe National Institutes of Health (NIH) who co-authored thepaper with Nussbaum. "It allows us to unveil and uncovernew functions. These mice didn't breathe. That was a realsurprise. The tests that we ran said that there was enoughcollagen [the structural "matrix" that holds tissuestogether].

"We asked 'why didn't these mice breathe, what wasdifferent about their lungs?' "​ Levine continued, "and Ithink we may have unmasked a new function for vitamin C. Itcould have implications. We have more work to do."​The only proven human requirement for vitamin C, orascorbic acid, is to prevent scurvy, a diseasecharacterised by bleeding gums, anaemia, skin haemorrhages,and death, first discovered in 18th century maritime sailorswhen their diet was found to be deprived of vitamin C-richfruit.

The normal recommended daily allowance (RDA) for vitamin Cfor women is 75 mg daily, which is increased by 10 mgduring pregnancy, a little more than the amount in theaverage-sized orange. Lactating (breast-feeding) womenshould take 95 mg. But overall vitamin C intake can varygreatly in the general public, ranging anywhere from 20 mgto 10,000 mg per day.

Knowing that 20 per cent of the population consumes lessthan the recommended dietary allowance (RDA) for vitamin Cintake, Levine said the study has greater implications forwhat happens when there is a vitamin C deficiency, ratherthan what occurs with the devastating effect in mice of atotal absence of vitamin C. Since a low vitamin C level hasno dramatic symptoms - at times only simple fatigue - theeffects of that could remain undetected.

"What is the consequence of a low vitamin C level [duringpregnancy]?"​ said Levine. "What is the consequence forprematurity and central nervous system function? Theimplication of this work is that potential new functionsare revealed for vitamin C, especially for the lung andespecially at birth.

"But the implication, too, is that if defects exist theycan be fixed easily. For now, the message remains thatfruits and vegetables containing vitamin C have healthbenefits - a decreased risk for infection, cancer, stroke,hypertension, maybe even diabetes. And pregnant womenshould strive for five servings of fresh fruits andvegetables daily in their diet."

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