Research Interests
Dr. Combs is a leader in the area of selenium nutrition, metabolism and anti-carcinogenesis. His group conducted the first randomized, placebo-controlled clinical trial, finding that supplemental Se can reduce cancer risks in humans, particularly for cancers of the lung, prostate, and colon, as well as all cancers combined and total cancer mortality.
Selenium, an element with a chemistry similar to that of sulfur, was recognized as an essential nutrient only four decades ago, and for years the best characterized of its functions have been those involved in its nutritional "sparing" of vitamin E. It is now known to have essential functions in several enzymes in each of which it occurs as the amino acid selenocysteine. While these selenoenzymes are thought to discharge the nutritional roles of selenium, the fact that supranutritional levels of selenium are cancer-preventive suggests metabolic functions of other selenium metabolites.
Dr. Combs's research addresses the metabolism of selenium and the effects of selenium supplementation, genotype and other dietary factors. His group uses stable isotopes of selenium to study this metabolism in health adults. This also involves the development of new biomarkers of selenium status, including the characterization of non-protein bound selenium in plasma, the validation of buccal cell selenium and urinary selenium-metabolites to assess selenium status. Such parameters have relevance to both cancer risk reduction and safety assessment.
Dr. Combs also interested in the development of safe and effective foods that provide nutritionally relevant or cancer protective amounts of selenium, including those produced on high-selenium soils. He recently conducted a 12-mo. study to characterize plasma selenium concentration as a function of baseline plasma selenium level and level of daily selenium supplementation. This algorithm will be useful in determining the amount of food selenium necessary to reach a selenium status target based on minimization of cancer risk, and thus to provide empirical data for establishing cancer-protective food selenium levels.
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Research Accomplishments
- Demonstrated for the first time that supplemental selenium can substantially reduce the cancer risks of free-living Americans.
- Identified a low molecular weight form of selenium in plasma which responds to dietary selenium level.
- Demonstrated that non-absorbed selenium can affect the metabolism of the hind gut microbial community in ways that may be protective of tumor transformation of colonocytes.
- Documented the prevalence of calcium-deficiency rickets in southeastern Bangladesh.
- Demonstrated that rickets in Bangladesh can be prevented by food-based supplementation of calcium.
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