Dr. Jesse Gregory, Professor of Food Science and Human Nutrition at the University of Florida, is at the cutting-edge of research directed at understanding how variables of B-vitamin status (deficiency and/or excess) affect the rates of key metabolic processes and the resulting patterns of metabolites. What remains is to complete the connections between these outcomes, human health, and disease processes. The ultimate impact of his research is to provide a better understanding of how vitamins from the diet and supplements facilitate metabolic processes that can govern the development of disease at all stages of life. For example, it is believed that altered levels of vitamin B6 may have impacts on certain cancers, diabetes, inflammatory conditions like arthritis, and a number of cardiovascular diseases. Dr. Gregory is exploring what specific roles vitamins have in order to devise treatments for normalizing vitamin statuses. Such work can lead to refined nutritional recommendations, more effective development and use of dietary supplements, improved understanding of nutrient-disease interactions, and more effective diagnostic techniques for nutritional assessment by evaluating metabolic function. His research is novel in that it frequently works directly with human subjects in controlled studies. Further, his lab is among the first to evaluate the “big picture” of the effects of vitamin insufficiency and excess using metabolic methods.

Dr. Jesse Gregory, is researching the vitamins folate, B6, B12 and their interactions with one another, specifically as they function in one-carbon metabolism, which leads to the creation of nucleotides (DNA building blocks) and single-carbon units, which are involved in biochemical reactions that function in many aspects of cellular regulation. Studies have shown that chronic dietary insufficiencies of these vitamins are associated with risk of chronic and degenerative disease (including cardiovascular disease, stroke, cancer, and potentially Alzheimer’s and diabetes), and Dr. Gregory is interested in further exploring what goes wrong in deficiency, and what happens in excess. There are currently very clear linkages between the adequacy of  intake of vitamins and different chronic diseases, but more information is needed regarding the processes involved before specific conclusions can be drawn. The common denominator between these factors seems to be one carbon metabolism, which is where Dr. Gregory has focused much of his research. Because some of the mechanisms and their nutritional control are not fully understood, his research focuses on the development and use of novel methods to determine rates of these metabolic processes concurrent with state-of-the-art analyses of the patterns of metabolites to provide both in-depth and more global views of metabolic function. An important offshoot of this work is the development of new diagnostic tools for assessing nutritional adequacy on the basis of novel metabolic indicators.

Dr. Gregory has new current research needing support:

1. Determination of the effects of vitamin B12 insufficiency on rates of metabolic processes and the development of novel biomarkers and assessment tools for determining vitamin B12 deficiency.

   a. Among the elderly, the body tends to absorb vitamin B12 less efficiently, leading to common levels of low B12 in older individuals. Low B12 levels eventually result in anemia (which is easily diagnosed), or a greater consequence of chronic deficiency, which can cause neurological complications, including impaired cognitive function. Dr. Gregory is interested in developing ways for diagnosing vitamin B12 deficiency; many of the current tools are lacking in sensitivity and/or specificity. He is proposing to examining groups of humans that are low or normal vitamin B12 status and determining patterns of metabolites that can be used as biomarkers. He is interested in exploring what functions can be restored through supplementation to bring levels of vitamin B12 back to healthy normal levels.

2. Determining the consequences of high intakes of folic acid.

   a. Folic acid is commonly found in a large number of fortified foods and supplements, which have become critical elements of the American diet. The beneficial aspect is that higher intake in the population lowers the risk of a form of neural-tube birth defects, such as spina bifida, which is the reason why many grain-based foods are fortified with the vitamin. Folic acid is generally beneficial to the body, but can have harmful effects when levels of vitamin B12 are sub-par. In some elderly individuals who have inadequate vitamin B12 status, the potential exists to be harmed by the excessive intake of folic acid. In addition, there are concerns among some scientists that other risks exist regarding the development of certain cancers. At the present time, it is unclear how serious of health risk high intake of folic acid presents. Dr. Gregory is designing experiments to better understand the effects and, thus, lead to a better understanding of the metabolic properties and safe levels of folic acid intake.

3. Influence of vitamin B6 insufficiency on amino acid metabolism and insulin resistance in obesity.

   a. There is sufficient evidence from national government surveys that low vitamin B6 nutritional status is more common in obese individuals. It is also known that, among the many metabolic issues in obesity, there is impaired metabolism of branched-chain amino acids (BCAAs) which leads to BCAA elevation in blood.  Dr. Gregory has formulated the hypothesis that since vitamin B6 is required in the metabolism of branched-chain amino acids (BCAAs), whose metabolism is already impaired in obesity, that obese people with low levels of vitamin B6 will have further impairment in their BCAA metabolism. Because BCAA elevation in obesity is associated with insulin resistance, low levels of vitamin B6 could contribute to their diabetes risk. Dr. Gregory is working to secure funding to test this hypothesis, which could lead to a clearer understanding of this aspect of nutrition and disease for this population.

4. Development of a novel diagnostic tool for vitamin B6 insufficiency based on patterns of metabolites.

   a. Within the last few years, Dr. Gregory’s lab has worked in the areas of metabolite profiling and metabolomics, measuring large patterns of metabolites, rather than single-compound indicators typically of nutritional adequacy, such as the widely used measurement for B6 assessment of pyridoxal phosphate in blood samples. The patterns of such metabolites are then subjected to advanced statistical analysis to evaluate what changes occur as a function of vitamin B6 adequacy or insufficiency. He has found evidence that there are certain metabolites in the blood that respond in consistent ways that reflect the metabolic signature of vitamin B6 insufficiency. Dr. Gregory would like to develop a simple mathematical tool that would take the responses of a handful of metabolites and input those responses into a formula that will calculate the functional vitamin B6 status of a person: whether they have adequate B6 levels, are moderately deficient, or severely deficient, based on those indicators. Measuring a collection of factors, rather than levels of a single indicator, is vastly more informative, and would be a functional diagnostic tool for determining nutritional status. The sensitivity and specificity of such a tool can then be evaluated in samples from existing large-scale studies in which health outcomes (including cardiovascular disease) and certain other nutritional indicators are already known.

5. Consequence of the association of inflammatory conditions with low vitamin B6 status.

   a. A colleague of Dr. Gregory’s has made the observation that a wide range of inflammatory conditions, including cardiovascular disease, rheumatoid arthritis, and a number of others involving systemic inflammation, are related to the reduced status of vitamin B6. There are hypotheses suggesting the cause, but concrete information is still limited. As an experienced investigator in this area of research, Dr. Gregory would like to address the question and potential outcomes of vitamin B6 insufficiency. If an induced vitamin B6 deficiency is the cause, along with inflammation, Dr. Gregory would design experiments to uncover ways of restoring healthy B6 status.