With today's easy availability of dietary supplements, it is worth remembering the health impact of early vitamin research: pellagra, scurvy, beriberi, rickets and other diseases of vitamin deficiency were virtually eliminated overnight when widespread dietary changes were made or vitamin supplements became available.

Today in the United States, outright vitamin deficiencies are unusual, but vitamins continue to be a fundamental focus of nutrition research. While some of their functions remain elusive, delineating vitamins' metabolic pathways provides insights into diverse diseases. For example, common problems of the elderly increasingly are recognized as being exacerbated by vitamin deficiencies, possibly because of poorer absorption or utilization.

Ralph Green, chair of the UC Davis School of Medicine's Department of Medical Pathology, and Joshua Miller, associate adjunct professor working with Green, are better defining the links of three B-group vitamins to disease. These water-soluble vitamins serve as critical cofactors in a number of metabolic functions, as well as in normal DNA synthesis.

A deficiency of vitamin B12 — essential for red blood cell formation — causes anemia, as well as gastrointestinal and cardiovascular problems and "a textbook of neurological complications," according to Green. In the U.S., the most common cause of vitamin B12 deficiency is a lack of intrinsic factor needed to absorb the vitamin from the gastrointestinal tract. The resulting condition, "pernicious anemia," was fatal before vitamin B12 supplements became available.

In work spearheaded by Lindsay Allen, emeritus professor in the Department of Nutrition and director of the Western Human Nutrition Research Center, Green and Miller have challenged medical dogma that pernicious anemia occurs predominantly in northern Europeans. They've gathered epidemiological data in Latin America and African countries, and found that not only is it at least as common in people in less-developed countries, but it starts at younger ages.

One difficulty that has plagued clinicians and researchers is measuring an individual's ability to absorb vitamin B12. Current methods require labeling B12 with cobalt 57 (⁵⁷Co), a potentially harmful radioactive tracer. Miller and Green are collaborating with Lawrence Livermore National Laboratory and the UC Davis Division of Biological Sciences' Section of Microbiology to develop a better technique. The new test uses vitamin B12 labeled with carbon 14 (¹⁴C), a much safer natural isotope also used in carbon dating. Lawrence Livermore's ultra-sensitive accelerator mass spectrometer enables them to assess extremely small samples of body fluids, further reducing risk.

"The new assay promises to revolutionize the whole field of B12 absorption studies," says Green. They are already looking toward labeling various food sources of vitamin B12 with ¹⁴C, and then measuring its presence after the food is eaten by research subjects. This will provide new information on the bioavailability of B12 in different foods, something that has been difficult to ascertain accurately.

Another prominent UC Davis nutrition researcher, Charles H. Halsted, also has a special interest in another B vitamin — more commonly known as folic acid — and its role in alcoholism and alcoholic liver disease.

Professor emeritus of internal medicine and director of the Clinical Nutrition Research Unit, Halsted is about to launch a placebo-controlled study at the new General Clinical Research Center, which houses clinical investigations for both the UC Davis School of Medicine and the Sacramento Veterans Affairs Medical Center. He will evaluate the potential therapeutic effects of a nutritional supplement, S-adenosyl-methionine (SAMe), a molecule normally produced in reactions involving folic acid, in patients with alcoholic liver disease. His project is based on his other experimental studies that show that SAMe is lowered by alcohol feeding and that SAMe has a positive effect in preventing the development of alcoholic liver disease.

"Alcoholism — or addiction to alcohol — is not a rare disease. It affects at least 5 percent of Americans and about 1 to 2 percent of our population develops alcoholic liver disease, which is typically fatal," Halsted says. "A dietary supplement that can prevent the progression of alcoholic liver disease and even allow the liver to heal once the process is started could make a big difference in the lives of many. Combined with an effective abstinence program, SAMe may give patients with alcoholic liver disease, who were once considered hopeless, a chance for a new start."