Curtiss D. Hunt supervises the Nutritional Histopathology Laboratory andoversees the Electron Microscope Laboratory. Dr. Hunt's research interestsare in trace element nutrition dealing primarily with boron. Dr. Hunt'sinterest in boron nutrition began in 1983 with the serendipitous observationthat chicks inadvertently made vitamin D deficient responded well to theaddition of boron to their diet. During further experimentation, Dr. Huntfound that vitamin D deficient chicks, exhibiting the usual signs of poorbone development, showed a marked improvement in bone structure when boronwas added to the low boron diet. These findings were the first evidencethat boron has a beneficial effect in animals, and by extrapolation, inhumans. Furthermore, the findings suggested that boron may be important inthe prevention of bone diseases of unknown cause, including osteoporosis andrheumatoid arthritis. There is now considerable evidence that boroninteracts with vitamin D to affect bone structure.

Dr. Hunt is pursuing the hypothesis that boron prevents inflammatorydiseases including rheumatoid arthritis and asthma. Boron is known toinhibit the activity of two classes of enzymes directly involved in theinflammatory process, a normal process that focuses the body's defenses at asite of injury or infection. Excessive enzyme activity leads to inflammatorydisease. It may be that boron status can influence the development ofinflammatory disease. Dr. Hunt is obtaining information from animal modelsto assess the connection between boron deficiency and debilitatinginflammatory disease. His laboratory has found that dietary boron reducesthe incidence and severity of inflammation in animal models. These findingswill be used to test the effects of dietary boron in persons suffering fromrheumatoid arthritis.

Other findings from Dr. Hunt's earlier boron research led him to concludethat boron is an important regulator of energy metabolism. Because boronchanges the amount of energy molecules in the blood, he examined whetherboron changes the way the body releases and circulates the hormone calledinsulin. Insulin is made and released from the pancreas and regulates howmuch sugar is taken out of the blood and put into cells. He removed theboron from the diets of chicks and rats and then put some back in todetermine whether boron changed how insulin was released from the pancreasand distributed in the blood. He found that the amount of insulin in theblood, but not the amount of glucose in the blood, drops when boron is putin the diet. This means that small amounts of boron in the diet may helpinsulin work more effectively in controlling the amount of glucose in theblood. This finding may further our understanding of complex diseases suchas type 2 diabetes.

It is very difficult to determine how animals and humans use boron becauseit is very hard to detect when boron is attached to molecules. Dr. Huntdeveloped a new method with capillary electrophoresis to distinguishmolecules that attach to boron from those that do not. He used the methodto discover four molecules that have much greater attraction for boron thanany previously known molecules present in humans and animals. Three ofthese molecules (diadenosine hexa-, penta-, and tetra-phosphate) are of arecently discovered type with many functions including control of bloodclotting. The fourth (S-adenosylmethionine) is significant in many basicbiologic processes and may be used to prevent or treat arthritis,depression, and liver disease. His results suggest that these molecules mayneed boron to perform their normal functions.

Because of the importance of boron in animal and human nutrition, it isreasonable to determine the normal sources of dietary boron. Dr. Hunt andcolleagues recently completed the analysis of boron content of 234 foodsknown to constitute 80% of the typical American diet. These analysesconfirmed that fruits, vegetables and legumes are major sources of boron,with peanuts having the highest boron content. This study also indicatedthat boron consumption declines nearly four fold between infancy andadulthood when body weights are taken into account, a finding that mayrelate to increased bone disorders with age.

Co-produced the first evidence that boron has an essential physiologicalrole in the chick. The chick responded to physiological amounts of dietaryboron as indicated by changes in growth and tibial epiphysial growth platecalcification. Because the chick is a good model for studying human nutrientrequirements, the research findings suggest that boron nutriture influencesbone growth and development in humans.

Demonstrated that amounts of dietary boron present in typical dietsinfluence the effect of certain nutritional stressors (inadequate magnesium,calcium or cholecalciferol) on various morphological and biochemicalindices. For example, in the vitamin D-deficient chick, supplemental dietaryboron added to a boron-low diet enhances growth at the expense of cartilagecalcification when dietary magnesium is inadequate and slows growth to thebenefit of calcification when dietary magnesium is adequate. Dietary borondoubles plasma 1,25-dihydroxyvitamin D3 concentrations in chicks fedlow-boron diets that contain inadequate amounts of vitamin D. These findingsindicate that amounts of boron found in typical diets interact withregulators of mineral metabolism to affect bone structure.

Provided the first evidence for the homeostatic control of boron through theconstruction and use of boron-low diets. Postmenopausal women housed in ametabolic unit for 199 d and fed a basal diet (conventional Western foods)that supplied an average of 0.36 mg B/d (and 109 or 340 mg Mg, and <0.10 mgor 1000 mg Al/2000 kcal) then supplemented with 2.87 mg B/d (similar toamounts found in diets luxuriant in fruits, vegetables, nuts, and legumes)did not exhibit an increase in boron retention. The boron supplementation,compared to the boron-low treatment represented a 9.0-fold increase indietary boron but yielded only a 1.5-fold increase in plasma boronconcentrations. Lack of boron accumulation and relatively small changes inboron blood values during a substantial increase in dietary boron supportthe concept of boron homeostasis.

Demonstrated that amounts of dietary boron present in typical dietsinfluence animal energy substrate utilization. The effects of boron are morepronounced when the animal is physiologically stressed by a variety ofnutritional factors. For example, in vitamin D-deficient chicks fed aboron-low diet, dietary boron returns plasma glucose to concentrationsexhibited by vitamin D-adequate chicks. In chicks given a similar dietarytreatment, dietary boron substantially decreases peak in situ pancreaticinsulin secretion following a glucose load. These findings led to thehypothesis that boron acts as a regulator of energy substrate utilization byquenching the activity of some enzymes and/or stabilizing reactivecompounds. The findings are of use in studies dealing with inflammatoryresponses, oxidative metabolism and free radical production.

Discovered that physiological amounts of dietary boron improves the humoralimmune response to injected antigens. For example, dietary boron greatlyaugments serum antibody concentrations in both chicks and rats challengedwith antigens. In rats injected with an adjuvant that induces experimentalarthritis, dietary boron alleviates bone joint swelling and reduces theincidence of joint inflammation thirty days after injection. Findings fromin vitro studies with isolated splenic cells indicate that boron affectscell proliferation. The response of splenic cells isolated from chicks fedthe basal diet and incubated with mitogens differs according to the amountof boron added during incubation. Lower concentrations of boron stimulatesplenocyte proliferation in the presence of certain amounts of a T-cellmitogen whereas higher concentrations inhibit proliferation. The mechanismby which dietary boron modulates the inflammatory response is underinvestigation.

Determined that the daily intake of boron usually differs considerablybetween any two individuals by analyzing a variety of typical Western foodsand personal care products. The concentration of boron in water variesconsiderably according to geographical source; at some locations the boronin drinking water and water-based beverages may account for most of thetotal dietary boron intake. Individual food preference greatly influencesdaily intake of boron; fruits, vegetables, tubers, and legumes haverelatively much higher concentrations of boron than do cereal grains oranimal tissues and fluids. Also, boron is a significant contaminant of, ormajor ingredient of, many different personal care products.

Demonstrated that moderate copper deficiency during pregnancy and lactationimpairs development of some brain structures involved with learning andmemory. Female rats were fed one of several test diets that containeddifferent amounts of inadequate copper during the pregnancy and nursing oftheir young. At weaning, the dentate gyrus and hippocampus, areas of whichdevelop postnatally, were found to be susceptible to copper deficiency. Allcopper deficiency-induced alterations of these brain structures wereconsistent with slowed cell maturation. Because learning and memory arevital functions of the brain and because dietary copper influences thedevelopment of some critical structures of the brain, research is underwayto determine whether copper deficiency-induced alterations in braindevelopment are transient or permanent.

Demonstrated that zinc depletion in humans as short as 36 days perturbsindices of human male fertility. Compared to when they were consuming 10 mgZn/day, male volunteers consuming 1.4 mg Zn/day for 36 days had lower semenvolumes; lower serum testosterone concentrations; lower total ejaculatoryzinc loss; and elevated seminal phosphorus, sodium, and iron concentrations.Seminal loss accounted for 9% of total body zinc loss when 1.4 mg Zn/day wasconsumed. The findings indicate that the zinc pool required for normalspermatozoon development is maintained while the pool required for seminalfluid production or normally transferred to the seminal fluid is utilized bythe body elsewhere. The findings also provide a real baseline forcalculating seminal zinc loss in human zinc balance studies.

Determined typical daily boron intakes of toddlers, adolescents, youngadults, and mature individuals in the US to provide one kind of evidenceneeded to establish an Recommended Dietary Allowance for boron. The 234 corefoods identified in the FDA Total Diet Study that represent approximately90% or more of the weight of the foods usually consumed were purchasedlocally and prepared for consumption as needed. Triplicate food samples werewet digested prior to boron analysis by inductively coupled argon plasma.Milk and milk products, juices, and beverages were the largest contributorsto dietary boron. Total boron content of average daily diets ranged from 548(g for toddlers (2 yr old) to 883 (g for mature males (60-65 yr old),excluding tap water contributions. Toddlers consumed 3.7 times more boronthan mature males when adjusted for body weight and consumed the diet withthe highest boron density (1.8 g/kJ [0.43 g/kcal]). Adolescent femalesconsumed a diet with the lowest boron density (1.12 g/k [0.26 g/kcal]).These estimations of boron in US diets are consistent with reports in theliterature that normal adult daily boron intakes are near 1 mg.

Led a team that identified the biological compounds in humans with thehighest currently known affinities for boron. They are S-adenosylmethionine(SAM) and the diadenosine polyphosphates (ApxA) Ap3A, Ap4A, Ap5A, and Ap6A.SAM is the predominant methyl donor in biological methylations and is aversatile cofactor in a variety of physiologic processes. ApnA moleculesfunction as signal nucleotides associated with platelet aggregation andneuronal response and are putative “alarmones” which reportedly regulatecell proliferation, stress response, and DNA repair. The findings giveindirect evidence that boron may function in gene expression and bloodcoagulation.

Led a team to discover that dietary boron reduces plasma insulin but doesnot change glucose concentrations and does so regardless of vitamin D3 ormagnesium status. These results suggest that boron may help reduce theamount of insulin needed to maintain plasma glucose. This finding mayfurther understanding of complex diseases such as type 2 diabetes.