University of Connecticut |
Richard M. Clark, Ph.D.ProfessorDepartment of Nutritional Sciences Website: www.criticalthinking.uconn.edu BackgroundRichard M. Clark, Professor of Nutrition, earned both bachelor's and master's degrees from the University of New Hampshire in Animal Sciences, then a Ph.D. degree in Animal Nutrition from Virginia Polytechnic and State University. His research interest area is currently focused on digestion and absorption of lipids and lipid-soluble nutrients. Dr Clark and his students have published more than fifty full-length articles based on research supported by the National Institute of Health and U.S. Department of Agriculture. Graduate students trained by Dr Clark are now working at Mystic Aquarium, National Cancer Institute, Connecticut Department of Health Services, the Mayo Clinic as well as other colleges and universities. Dr Clark has been a member of several college and university committees, with most assignments relating to teaching or student welfare. He currently advises 10-15 undergraduate students and is the Department's Advisor for students participating in the University Honors Program. Dr Clark received the Donald M. Kinsman Award for Excellence in Undergraduate Teaching and the CANR Alumni Teaching Award, and a USDA National Teaching Award. TeachingTeaching is my avocation. Besides the usual classroom teaching, I have been experimenting with problem based learning in the Honors Colloquium in Nutrition and with the use of multimedia in the undergraduate Nutritional Assessment course. Outside the classroom I enjoy working with students and in the past have served as the faculty advisor for the Nutrition Club, the Men's Lacrosse Club, and have been a member of the PreMed advisory board, and active in the University Honors Program. Undergraduate
Graduate
Overview of Research InterestsMy research is primarily directed toward the study of digestion, absorption and transport of lipids. Specific research include:
The major purpose of my research is to train graduate students and a limited number of highly motivated undergraduates. Most of my research relies on the use of whole-animal models. During the past decade, students in my laboratory have studied nutritional problems utilizing rats, rabbits, calves, sheep, seals and humans. Graduate students trained in my laboratory generally develop a secondary skill area such as surgery, statistics or a specific analytical technique. Recent Research PublicationsYou can click on the names of graduate students who completed their degrees with Dr. Clark and a JavaScript window will appear with information on their palcement after leaving the University of Connecticut. You can also view abstracts of the papers listed by clicking on [abstract].
Excess Vitamin E Decreases Canthaxanthin Absorption in the Rat Susan Hageman, Li She, Harold C. Furr and Richard M. Clark Abstract The recent attention given to the possible role of alpha-tocopherol (a-Toc) and carotenoids in the prevention and treatment of a variety of illnesses has resulted in segments of the population increasing their consumption of these nutrient/antioxidants. Once consumed a-Toc and carotenoids are thought to follow the same absorptive pathway and may influence each other’s absorption, particularly when taken in large doses. The purpose of this study was to determine if a-Toc and the carotenoid ,canthaxanthin (CTX), interact during absorption. Rats were intraduodenally infused with corn oil emulsions containing combinations of a-Toc (0 or 300 umol/L) and CTX (5, 10, 15, 20 umol/L) in a 2x4 factorial arrangement. Absorption was determined by measuring recovery of CTX and a-Toc in the mesenteric lymph. The amount of CTX in the lymph increased significantly with the amount infused into the duodenum. The overall efficiency of CTX absorption from emulsions without a-Toc averaged 12 % with individual animals having a range of 8 to 18%. Efficiency of absorption was not related to concentration of CTX infused. When a-Toc (300 umol/L) was added to the oil emulsion, the absorption of CTX was decreased by at least 50 %. Recovery of a-Toc in the lymph averaged approximately 10 % and was not affected by CTX. These results suggest that concurrent consumption of a large dose of a-Toc may influence carotenoid bioavailability. Lipids 1999;34:627-631. A Comparison of Lycopene and Canthaxanthin Absorption:Using the Rat to Study the Absorption of Non-Provitamin A Carotenoids. Richard M. Clark, Lili Yao, Li She, and Harold C. Furr. Abstract The purpose of this study was to validate the use of the mesenteric lymph duct cannulated rat to study the absorption of carotenoids which do not have provitamin A activity. The absorption of two carotenoids, a hydrocarbon carotenoid (lycopene) and a xanthophyll carotenoid (canthaxanthin), were investigated. In the first experiment, lipid emulsions containing lycopene (LYC) or canthaxanthin (CTX) were continuously infused into the duodenum, and lymph was collectedfor analysis at 2 h intervaals. The time course for absorption of carotenoids and triacylglycerol (TAG) was similar. Carotenoids and TAG reached steady-state concentrations in the lymph by 6 h. There was no evidence for a delayed release of either carotenoids from the intestine relative to TAG. During a second experiment, emulsions containing increasing concentrations of LYC or CTX (5, 10, 15, 20 umol/L0 were infused. The LYC and CTX in the lymph increased in a dose dependent manner. The average efficiency of CTX absorption was 16% while the efficiency of LYC absorption averaged only 6%. Efficiency of carotenoid absorption was not related to concentration infused. Finally, to test whether LYC and CTX interact during absorption both were added to a lipid emulsion at equal concentrations (20 umol/L) and infused. The carotenoids did not significantly affect each other's absorption. These results demonstrate the usefulness of the rat as an animal model to study the absorption of non-provitamin A carotenoids. Lipids 1998;33:159-163. Intestinal Absorption and Tissue Distribution of Carotenoids Harold C. Furr and Richard M. Clark Abstract Human metabolism of carotenoids is of interest not only because of the provitamin A function of certain carotenoids, but also because these compounds have been associated with reducing risk of certain cancers and chronic diseases. Full understanding of carotenoid metabolism is complicated by a number of factors; variations in physiochemical properies among carotenoids; altered carotenoid utilization as a result of the normal vicissitudes of lipid absorption and transport; divergence in metabolic fate within the intestinal enterocyte (especially carotenoid cleavage to retinoids); differences in packaging and transport in lipoproteins; dissimilarity in tissue uptake of specific carotenoids; and the possible isomerization of carotenoids within tissues. Hampering research is the lack of animal models that perfectly mimic human carotenoid metabolism and the limited number of carotenoids approved for human consumption in a pure form. It is clear, however, that diet affects carotenoid absorption. The efficient digestion and absorption of dietary fat, as well as the presence of bile salt micelles, is essential for carotenoid absorption. Competition among carotenoids and other dietary components for absorption, transport, and tissue uptake is documented but needs further research. From limited data it seems that the more polar carotenoids (xanthophylls) may be absorbed more efficiently that are the carotenes (hydrocarbon carotenoids). The mechanism in humans for the phenomenon of "nonresponders" to oral doses of beta-carotene requires further study to determine whether it is an effects of inefficient absorption or of intestinal cleavage of beta-carotene. The delayed maxima in plasma carotenoid concentration after ingestion, relative to plasma triacylglycerol, are expainable as secondary secretion of carotenoids transferred to other lipoproteins after chylomicron clearance. The site and degree of isomerization of carotenoids after consumption has not yet been defined. In this article the absorption, transport, and tissue uptake of carotenoids will be reviewed and possible differences among carotenoids and factors influencing their utilization will be discussed. J Nutr Biochem 1997;8:364-377. Long Chain Polyunsaturated Fatty Acids and Bovine Luteal Cell Function T. Hinckley, Sr., R. M. Clark, S.L. Bushmich, and R.A. Milvae Abstract Experiments were conducted to determine the effects of exogenous polyunsaturated fatty acids (PUFA) on the production of progesterone and prostanoids by dispersed bovine luteal cells and to characterize endogenous luteal fatty acids throughout the estrous cycle. The addition of eicosapentaenoic acid (20:5, n3) resulted in a dose dependent reduction of progesterone production and an increase in production of prostaglandin PGF2alpha (p<0.05). Nordihydroguaiaretic acid abolished the inhibitory effects of 20:5, n3 on progesterone production, while inomethacin did not alter these effects. The addition of 10 ug docoahenaenoic acid (22:6, n3) resulted in supression of progesterone synthesis (p<0.05) and reduction of PGF2alpha synthesis. The addition of 0.1, 1 and 10 ug docosatetraenoic acid (22:4, n6) inhibited basal progesterone production, whereas only the highest dose decreased LH-stimulated synthesis of progesterone. The addition of 22:4, n6 resulted in increased PGF2alpha synthesis (p<0.05) and in lower synthesis of prostacyclin (p<0.05). Variations in luteal fatty acids were characterized throughout the estrous cycle. The percentages and ratios of PUFA were altered throughout the estrous cycle. In summary, PUFA have potent inhibitory effects on the production of progesterone and PGI2 in vitro and may play a role in bovine luteal cell function by mechanisms yet to be determined. Biol Reprod 1996;55:445-449. Study of Vitamin A Supplementation in Captive Northern Fur Seals (Callorhinus ursinus)and Its Effect on Serum Vitamin ELisa Mazzaro, J. Lawrence Dunn, Harold Furr and Richard M. Clark Abstract Two experiments were conducted to determine the effect of vitamin A supplentation on serum vitamin E in adult nothern fur seals (Callorhinus ursinus). In the first experiment five animals received, in addition to theeir routine dietary multivitamin supplement, a high-level vitamin A supplement (53 umol retinyl palmitate/d) for 30 d. Five seals consuming their routine dietary supplement served as controls. Serum vitamin E decreased significantly in animals receiving high-level vitamin A supplements. At the end of 30 d serum vitamin E averaged 18.6 ug/mL in the control animals and 13.4 ug/mL in the animals receiving the high-level vitamin A supplements. In experiment 2 ten animals received the high level vitamin A supplenet for 60 d. After 30 d, serum vitamin E levels were reduced, but by 60 d had returned to baseline levels. However, the ratio of serum vitamin E to phospholipid, another index of vitamin E staus, remained decreased. Although, the exact mechanism of intereaction is inknown, this study shows that when providing vitamin supplements for captive pinnipeds, vitamin interactions must be considered. The vitamin A supplementation currently used by some institutions seems unnecessary and may have detrimental effects on vitamin E status. Marine Mammal Science 1995;11:545-553. Vitamin A Plasma Kinetics in Norther Fur Seals (Callorhinus ursinus), Using Vitamin A-2 as a Tracer Lisa Mazzaro, J. Lawrence Dunn, Harold Furr and Richard M. Clark Abstract Vitamin A-2 (3,4-didehydroretinol), a natural analog of retinol, was used to determine the plasma kinetics of vitamin A in two northern fur seals (Callorhinus ursinus) receiving two levels of vitamin A supplements. After a single dose, the time required to reach a maximum plasma vitamin A-2 concentration for both subjects was approximately 2 h, which is much less than the 8-12 h observed with humans. The level of vitamin A supplementation did not affect base-line plasma retinol concentrations or plasma kinetics. The mean sojour time, the average time spent by a molecule of vitamin A in the body before being lost, was 40 days for one animal and 73 days for the other. The daily vitamin A requirement estimated from the disposal rate was 0.32-0.64 umol per day for the two animals. The presumed upper safe level was calculated at 1.3 - 6.4 umol vitamin A per day. It would appear that the fish diet commonly provided to these animals can meet their vitamin A reqirements. Supplementation may only be warranted to offset vitamin loss during storage and handling of the food. However, a conservative approach to supplementation should be used as chronic vitamin A toxicity is a danger. Can J Zoo 1995;73:10-14. Effect of Hyperinsulinemia on Growth in the Fetal Rabbit David G. Chaffin, Richard M. Clark, David McCracken and A.F. Philipps. Abstract Insulin is an important regulatory hormone in the control of fetal growth. In a rabbit model, a non-ruminant species, the effects of insulin deprivation on glucose, growth and protein metabolism were studied. The fetuses of 10 pregnant New Zealand white rabbits in one uterine horn received a subcutaneous injection on day 25 of gestation (term = 30 days) of 0.1 mg streptozotocin (STZ)/gm fetal weight. The fetuses in the opposite horn received a sham injection of buffer. The dams were killed on day 29. The fetal infulin concentration was depressed by 38% , and the serum glucose concentration was elevated by 28% in animals given STZ when compared to control animals. Fetal weights, carcass weights and skeletal growth, as measured by crown-rump length and tibial length of STZ-treated fetuses, were significantly reduced by 7-13%. However, organ weights were not significantly different, except for the kidneys which were 17% lighter. Protein and mineral contents of the carcasses were also reduced compared to the control fetuses. Thus, insulin deprivation in fetal rabbits resulted in significant growth impairment in a pattern similar to that of human asymmetric intrauterine growth retardation. Biol Neonate 1995;67:186-193. Lymphatic Fatty Acids from Rats Fed Human Milk and Formula Supplemented with Fish Oil Richard M. Clark and Li She Abstract Absorption of long-chain polyunsaturated fatty acids from human milk and formula supplemented with fish oil was studied to determine if the distribution route into lymphatic triaculglycerol (TAG) and phospholipid (PL) varies with the dietary source. Rats were intraduoendally infused with human milk or formula containing graded amounts of fish oil (0, 0.5, or 1.0 g/100 mL), and the mesenteric lymph collected. Arachidonic acid (20:4n-6) levels in lymphatic TAG and PL were highest from animals fed human milk. In the animals infused with formula containing fish oil, as the amount of eicosapentaenoic acid (EPA, 20:5n-3) infused increased, there was essentially an equal increase in EPA associated lymphatic TAG and PL. Animals intraduodenally infused with human milk or formula without fish oil had only minor levels (less than 1%) of the EPA in the lymph. In the fish oil-treated animals, as the amount of docosahexaenoic acid (DHA, 22:6n-3) infused increased, there was a 16-fold increase in DHA associated with lymphatic TAG, but only a 3-fold increase in DHA associated with lymphatic PL. The highest level of DHA in rats infused with human milk was observed in lymphatic PL. Hence, fish oil can be added to formula as a source of long-chain polyunsaturated fatty acids, but the distribution of fatty acids into the lymphatic TAG and PL is not the same as that observed with human milk. Lipids 1995;30:673-676. |
News and UpdatesJune 16, 2008 – Research Study February 5, 2008 - "What's Happening"
Positions OpenAssistant Professor Lecturer |