"Though it is known that the antioxidant vitamins play a role in human health, the mechanisms are poorly understood," said Peter Sinclair, a VA researcher and research associate at Dartmouth Medical School. "This study may lead us to an understanding of how vitamin C behaves in a particular disease."
It is still unclear whether a deficiency of vitamin C is a contributing cause of the disorder or one of its effects.
PCT is the most common form of porphyria, a group of disorders that causes chemicals called porphyrins to accumulate in the body. Porphyrins are building blocks for the production of heme, an iron-containing substance found in all body tissues. In people with PCT, a critical enzyme in the liver becomes inactivated, interfering with the production of heme from its precursor porphyrins. As a result, the porphyrins build up in the liver, spill into the blood and are carried to the skin. Untreated, people with PCT and some other porphyrias develop blisters and skin damage when exposed to sunlight.
Excess alcohol consumption, oral contraceptives and exposure to dioxins, including those in the herbicide Agent Orange, have been known to trigger the disorder. A more common disorder known as hemochromatosis, which causes a dangerous buildup of iron in peoples' bodies, is linked to the same genetic defect as PCT. The most common treatment for both diseases is blood drawing, which decreases excess iron.
In the August study of people being treated for PCT, the researchers found that 11 out of 13 had very low vitamin C levels in their blood. Two patients whose blood levels were normal had been taking multivitamins. Possible explanations for the low values include dietary insufficiency, faulty metabolism of the vitamin, impaired absorption or increased turnover of the vitamin.
In earlier experiments the researchers found that adding vitamin C to cultures of chicken liver cells prevented the light-sensitive porphyrins from accumulating in the cells. In other studies in a special strain of rat which, like humans, gets vitamin C from dietary sources, the investigators found that normal levels of vitamin C prevented porphyrin accumulation in the liver. The vitamin C is thought to act at the step that causes the block in heme synthesis.
Though these preliminary studies suggest that increasing dietary levels of vitamin C may have a role in treatment of the human disease, Sinclair cautions that a potentially adverse effect must first be ruled out. "There is some clinical evidence that boosting levels of vitamin C in people with massive iron overload -- which itself causes problems -- might cause heart damage," said Sinclair. "What we hope to do now is determine whether vitamin C is effective in preventing porphyrin accumulation in patients and whether such treatment is safe."
In addition to Peter Sinclair, the research team included Nadia Gorman, Jacqueline Sinclair, Charles Honsinger and Margaret Karagas, all from Dartmouth Medical School; Steven Shedlofsky from the Kentucky VA and the University of Kentucky; and Karl Anderson from the University of Texas Medical Branch in Galveston.
The work was funded by the National Institutes of Health, the Department of Veterans Affairs, the United States Food and Drug Administration Office of Orphan Product Development, the American Porphyria Foundation, the National Center for Research Resources and the American Cancer Society.
CONTACTS:
Peter Sinclair
Associate Career Research Scientist,
VA Medical Center, White River Junction VT and
Research Associate Professor of Biochemistry and Pharmacology
Dartmouth Medical School
802/295-9363 extension 5657
or 802/584-3280
OR
Nancy Serrell
Science Writer
Dartmouth College
603/646-3661