A large study of more than 13,000 people found an inverse relationship between blood levels of vitamin C, also known as ascorbic acid, and the prevalence of gallbladder disease and undetected gallstones in women. In addition, the researchers observed that women who used vitamin C supplements had a lower prevalence of clinical gallbladder disease. The study appears in the latest issue of Archives of Internal Medicine.
"Although a few previous studies have shown a relationship between vitamin C and gallbladder disease, the size of our study and the collection of data on undetected gallstones strengthens the hypothesis that vitamin C levels may be an important risk factor for gallstone formation, at least among women," said Joel Simon, MD, MPH, UCSF assistant professor of medicine and epidemiology, and staff physician at the San Francisco Veterans Affairs Medical Center. "Because the study was conducted among a random sample of Americans, our results should be generalizable to the US population."
Building upon research done in animals that showed vitamin C-deficient guinea pigs frequently developed gallstones, the researchers hypothesized that the same relationship might hold true in humans. They specifically examined whether there was a relationship between ascorbic acid levels in the blood and the presence of asymptomatic gallstones - gallstones that are present but which haven't yet caused abdominal pain and therefore remain undetected.
Gallstones can form when bile, a liquid used to help the body digest dietary fat, becomes over-saturated with cholesterol. The cholesterol eventually hardens into stone-like material in the gallbladder forming gallstones. "Because vitamin C regulates the conversion of cholesterol into bile acids in experimental animals," said Simon, "we hypothesized that low levels of vitamin C may be a risk factor for human gallbladder disease as well."
To test their idea, the researchers analyzed data from 13,130 men and women enrolled in the Third National Health and Nutrition Examination Survey (NHANES III), conducted by the National Center for Health Statistics between 1988 and 1994. Serum ascorbic acid levels were measured using a modern analytic assay and abdominal ultrasound exams were used to test for gallstones.
Low levels of ascorbic acid in the bloodstream were associated with an increased prevalence of gallbladder disease in women, but not men, said Simon. Among women, an increase (0.5 mg/dL) in ascorbic acid levels was associated with an approximately 13 percent lower prevalence of symptomatic gallbladder disease. Additionally, the researchers found that using vitamin C supplements, or multiple vitamins containing vitamin C, was associated with a 34 percent lower prevalence of symptomatic gallbladder disease in women.
The researchers also found an association between vitamin C levels and asymptomatic gallstones. After excluding participants with known gallbladder disease and with abdominal pain characteristic of gallbladder disease, there were 9,650 participants available to test the relationship between ascorbic acid levels and asymptomatic gallstones.
Again, a 0.5 mg/dL increase in ascorbic acid levels was associated with an approximately 13 percent lower prevalence of asymptomatic gallstones in women, but not men. Because the participants did not know they had gallstones, changes in diet or behavior after learning of gallstones could not account for the results, said Simon. Finding the relationship between vitamin C and asymptomatic gallstones strengthens the hypothesis that low levels of vitamin C may be a risk factor for gallbladder disease, said Simon.
"Because the association between ascorbic acid and gallbladder disease has only been reported among women, there may be a biologic interaction between vitamin C and gender," said Simon. "However, it is also possible that we didn't detect an association in men because men get gallbladder disease less frequently than women thereby decreasing the ability to detect an association."
For women with very low vitamin C intakes, approximately one large orange per day could raise their vitamin C blood levels by 0.5 mg/dL, said Simon. For women who already are getting high enough amounts, an extra orange will make a smaller difference. Blood levels reach a plateau at approximately 1,000 mg of vitamin C per day, and vitamin C beyond that amount isn't absorbed well by the body, he said.
In addition to Simon, Esther Hudes, PhD, MPH, UCSF senior statistician in the department of epidemiology and biostatistics, co-authored the paper.