Vitamin C supplements can reduce levels of C-reactive protein, a marker of inflammation and chronic disease risk in humans, according to a new study led by researchers at the University of California, Berkeley.

Participants who took about 500 milligrams of vitamin C supplements per day saw a 24 per cent drop in plasma C-reactive protein (CRP) levels after two months. The study, published in the April issue of the Journal of the American College of Nutrition, is the first time vitamin C has been shown to decrease levels of CRP, a biomarker that has garnered increasing attention among health researchers in recent years.

"C-reactive protein is a marker of inflammation, and there is a growing body of evidence that chronic inflammation is linked to an increased risk of heart disease, diabetes and even Alzheimer's disease," said Gladys Block, UC Berkeley professor of epidemiology and public health nutrition and lead author of the study. "If our finding of vitamin C's ability to lower CRP is confirmed through other trials, vitamin C could become an important public health intervention."

Inflammation occurs as part of the body's defense against infection or injury. The body triggers the production of inflammatory cytokines, such as interleukin-6, that then set off the production of CRP by the liver.

"CRP levels can go up 100-fold within a short period of time as a reaction to an infection, but they then drop back down rapidly after the acute infection passes," said Christopher Jensen, a research scientist in Block's lab and co-author of the paper.

"It's not clear how vitamin C was able to lower CRP levels for people in this study," said Jensen. "One possibility is that vitamin C may be suppressing the production of cytokines, but that needs to be investigated in future studies."

The researchers say that long-term adverse health effects occur when inflammation persists at low levels. This chronic inflammation, with persistent low levels of CRP, has been found among smokers and Type 2 diabetics, as well as among overweight or obese persons. They say that scientists have only recently begun to understand such chronic inflammation as an important factor in disease.

"Several large studies have suggested that CRP may be a better predictor of heart disease than cholesterol levels, although this has been questioned," said Marion Dietrich, a UC Berkeley researcher in nutritional epidemiology and another co-author of the study. "Still, CRP is widely recognized as an important biomarker for inflammation. Elevated CRP concentrations have been found in obese people, indicating that obesity is associated with chronic inflammation. The association may help explain why overweight people are at increased risk for chronic disease development such as diabetes, heart disease or certain types of cancer."

For this study, researchers tested 160 healthy adults from Berkeley and Oakland, California, who either smoked or were exposed to second-hand smoke. The researchers adjusted for body mass index and baseline CRP concentrations. People who had high levels of CRP to start with, likely due to existing illness, were excluded from the study.

Participants were randomly assigned to receive a daily dose of a placebo, a vitamin C supplement of about 500 milligrams, or a mixture of antioxidants made up of vitamin C, vitamin E and alpha-lipoic acid. Neither the researchers nor the participants knew which group a subject belonged to in the double-blind study.

Plasma CRP levels were measured from blood samples before and after the two-month trial. Levels of CRP decreased significantly, by 24 percent, among participants who had taken the vitamin C pills when compared to those in the placebo group. For those taking the antioxidant mixture, levels of CRP decreased 4.7 percent compared to the placebo group, but the change was not statistically significant.

The researchers noted that in other studies, higher doses of vitamin E produced lower CRP levels among Type 2 diabetics and healthy individuals.

"We were surprised to find no statistical change in CRP levels among people taking the antioxidant mixture, while those taking the vitamin C supplement saw a significant 24 percent drop," said Block. "However, the only other study to administer vitamin C and vitamin E together also did not show an effect on CRP."

"It's possible that there is some interaction among the antioxidants that rendered the mixture less effective in reducing CRP levels, but that's not clear at this time," said Block. "This underscores the need to conduct further tests to confirm our findings."

The National Institutes of Health has awarded Block a grant to conduct another randomized trial of vitamin C and CRP levels. Block will begin recruiting participants for that trial in mid-May.

In the meantime, the researchers recommend that people eat plenty of fruits and vegetables to ensure they get a variety of nutrients in their diet. "I believe all adults should take a multivitamin every day," said Block. "As for vitamin C, a 500-milligram daily dose is safe, and I believe it is a very important nutrient. However, research to confirm these findings is needed before we can say it definitely reduces inflammation and reduces chronic disease risk."

Other co-authors of the study are Edward Norkus at Our Lady of Mercy Medical Center in New York; Mark Hudes at UC Berkeley's Department of Nutritional Sciences and Toxicology; and Lester Packer at the University of Southern California School of Pharmacy.

This research was supported by the University of California Tobacco-Related Disease Research Program and by the National Cancer Institute.