Dr.
Hunt was raised on a farm in southeastern Wyoming and obtained
a Master's (1976) and Doctor of Philosophy degree (1979)
in anatomy from the University of North Dakota. Dr. Hunt
has been affiliated with the USDA ARS Grand Forks Human
Nutrition Research Center through the University of North
Dakota since 1973. He joined the permanent staff of the
Center in 1987 to continue work in trace element nutrition
dealing primarily with boron and copper. He maintains direct
ties with the UND Department of Anatomy and Cell Biology
as an Adjunct Professor on their staff.
Dr.
Hunt supervises the Nutritional Histopathology Laboratory
and oversees the Electron Microscope Laboratory at the Center.
His research interests are in trace element nutrition dealing
primarily with boron and copper. Dr. Hunt's interest in
boron nutrition began in 1983 with the serendipitous observation
that chicks inadvertently made vitamin D deficient responded
well to the addition of boron to their diet. During further
experimentation, Dr. Hunt found that vitamin D deficient
chicks, exhibiting the usual signs of poor bone development,
showed a marked improvement in bone structure when boron
was added to the lowboron diet. These findings were
the first evidence that boron has a beneficial effect in
animals, and by extrapolation, in humans. Furthermore, the
findings suggested that boron may be important in the prevention
of bone diseases of unknown cause, including osteoporosis
and rheumatoid arthritis. There is now considerable evidence
that boron interacts with vitamin D to affect bone structure.
Dr.
Hunt is pursuing the hypothesis that boron prevents inflammatory
diseases including rheumatoid arthritis and asthma. Boron
is known to inhibit the activity of two classes of enzymes
directly involved in the inflammatory process, a normal
process that focuses the body's defenses at a site of injury
or infection. Excessive enzyme activity leads to inflammatory
disease. It may be that boron status can influence the development
of inflammatory disease. Dr. Hunt is obtaining information
from animal models to assess the connection between boron
deficiency and debilitating inflammatory disease. His laboratory
has found that dietary boron reduces the incidence and severity
of inflammation in animal models. These findings will be
used to test the effects of dietary boron in persons suffering
from rheumatoid arthritis.
Other
findings from Dr. Hunt's earlier boron research led him
to conclude that boron is an important regulator of energy
metabolism because he found that dietary boron changes the
amounts of glucose, insulin, and triglyceride present in
the blood, especially in the vitamin D deficient animal.
Insulin release is known to be dependent upon vitamin D.
thus, his group is actively studying the complex interactions
among boron, vitamin D, and insulin release. The findings
may further our understanding of the complex diseases such
as diabetes.
Because
of the importance of boron in animal and human nutrition,
it is reasonable to determine the normal sources of dietary
boron. Dr. Hunt and colleagues recently completed the analysis
of boron content of 234 foods known to constitute 80% of
the typical American diet. These analyses confirmed that
fruits, vegetables and legumes are major sources of boron,
with peanuts having the highest boron content. This study
also indicated that boron consumption declines nearly four
fold between infancy and adulthood when body weights are
taken into account, a finding that may relate to increased
bone disorders with age.
Dr.
Hunt also has an interest in the role of trace element status
on brain development. Brain development is adversely influenced
by inadequate nutriture, including copper, of the mother
during pregnancy. Studies with rats showed that inadequate
copper in the diet of the mother adversely affected the
development brain structures that are involved with learning
and memory. The inadequate copper nutriture of the mother
slowed the development of those structures in the offspring.
Because learning and memory are vital functions of the brain,
Dr. Hunt is conducting further research to determine whether
the developing brain can recover from inadequate copper
nutriture of the mother during late pregnancy and nursing.
Research
Accomplishments:
Co-produced
the first evidence that boron has an essential physiological
role in the chick. The chick responded to physiological
amounts of dietary boron as indicated by changes in growth
and tibial epiphysial growth plate calcification. Because
the chick is a good model for studying human nutrient
requirements, the research findings suggest that boron
nutriture influences bone growth and development in humans.
Demonstrated
that amounts of dietary boron present in typical diets
influence the effect of certain nutritional stressors
(inadequate magnesium, calcium or cholecalciferol) on
various morphological and biochemical indices. For example,
in the vitamin D-deficient chick, supplemental dietary
boron added to a boron-low diet enhances growth at the
expense of cartilage calcification when dietary magnesium
is inadequate and slows growth to the benefit of calcification
when dietary magnesium is adequate. Dietary boron doubles
plasma 1,25-dihydroxyvitamin D3 concentrations in chicks
fed low-boron diets that contain inadequate amounts of
vitamin D. These findings indicate that amounts of boron
found in typical diets interact with regulators of mineral
metabolism to affect bone structure.
Provided
the first evidence for the homeostatic control of boron
through the construction and use of boron-low diets. Postmenopausal
women housed in a metabolic 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 mg
or 1000 mg Al/2000 kcal) then supplemented with 2.87 mg
B/d (similar to amounts 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
in dietary boron but yielded only a 1.5-fold increase
in plasma boron concentrations. Lack of boron accumulation
and relatively small changes in boron blood values during
a substantial increase in dietary boron support the concept
of boron homeostasis.
Demonstrated
that amounts of dietary boron present in typical diets
influence animal energy substrate utilization. The effects
of boron are more pronounced when the animal is physiologically
stressed by a variety of nutritional factors. For example,
in vitamin D-deficient chicks fed a boron-low diet, dietary
boron returns plasma glucose to concentrations exhibited
by vitamin D-adequate chicks. In chicks given a similar
dietary treatment, dietary boron substantially decreases
peak in situ pancreatic insulin secretion following a
glucose load. These findings led to the hypothesis that
boron acts as a regulator of energy substrate utilization
by quenching the activity of some enzymes and/or stabilizing
reactive compounds. The findings are of use in studies
dealing with inflammatory responses, oxidative metabolism
and free radical production.
Discovered
that physiological amounts of dietary boron improves the
humoral immune response to injected antigens. For example,
dietary boron greatly augments serum antibody concentrations
in both chicks and rats challenged with antigens. In rats
injected with an adjuvant that induces experimental arthritis,
dietary boron alleviates bone joint swelling and reduces
the incidence of joint inflammation thirty days after
injection. Findings from in vitro studies with isolated
splenic cells indicate that boron affects cell proliferation.
The response of splenic cells isolated from chicks fed
the basal diet and incubated with mitogens differs according
to the amount of boron added during incubation. Lower
concentrations of boron stimulate splenocyte proliferation
in the presence of certain amounts of a T-cell mitogen
whereas higher concentrations inhibit proliferation. The
mechanism by which dietary boron modulates the inflammatory
response is under investigation.
Determined
that the daily intake of boron usually differs considerably
between any two individuals by analyzing a variety of
typical Western foods and personal care products. The
concentration of boron in water varies considerably according
to geographical source; at some locations the boron in
drinking water and water-based beverages may account for
most of the total dietary boron intake. Individual food
preference greatly influences daily intake of boron; fruits,
vegetables, tubers, and legumes have relatively much higher
concentrations of boron than do cereal grains or animal
tissues and fluids. Also, boron is a significant contaminant
of, or major ingredient of, many different personal care
products.
Demonstrated
that moderate copper deficiency during pregnancy and lactation
impairs development of some brain structures involved
with learning and memory. Female rats were fed one of
several test diets that contained different amounts of
inadequate copper during the pregnancy and nursing of
their young. At weaning, the dentate gyrus and hippocampus,
areas of which develop postnatally, were found to be susceptible
to copper deficiency. All copper deficiency-induced alterations
of these brain structures were consistent with slowed
cell maturation. Because learning and memory are vital
functions of the brain and because dietary copper influences
the development of some critical structures of the brain,
research is underway to determine whether copper deficiency-induced
alterations in brain development are transient or permanent.
Demonstrated
that zinc depletion in humans as short as 36 days perturbs
indices of human male fertility. Compared to when they
were consuming 10 mg Zn/day, male volunteers consuming
1.4 mg Zn/day for 36 days had lower semen volumes; lower
serum testosterone concentrations; lower total ejaculatory
zinc 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 was consumed.
The findings indicate that the zinc pool required for
normal spermatozoon development is maintained while the
pool required for seminal fluid production or normally
transferred to the seminal fluid is utilized by the body
elsewhere. The findings also provide a real baseline for
calculating seminal zinc loss in human zinc balance studies.
Determined
typical daily boron intakes of toddlers, adolescents,
young adults, and mature individuals in the US to provide
one kind of evidence needed to establish an Recommended
Dietary Allowance for boron. The 234 core foods identified
in the FDA Total Diet Study that represent approximately
90% or more of the weight of the foods usually consumed
were purchased locally and prepared for consumption as
needed. Triplicate food samples were wet digested prior
to boron analysis by inductively coupled argon plasma.
Milk and milk products, juices, and beverages were the
largest contributors to dietary boron. Total boron content
of average daily diets ranged from 548 (ug for toddlers
(2 yr old) to 883 (ug for mature males (60-65 yr old),
excluding tap water contributions. Toddlers consumed 3.7
times more boron than mature males when adjusted for body
weight and consumed the diet with the highest boron density
(1.8 ug/kJ [0.43 ug/kcal]). Adolescent females consumed
a diet with the lowest boron density (1.12 ug/k [0.26
ug/kcal]). These estimations of boron in US diets are
consistent with reports in the< literature that normal
adult daily boron intakes are near 1 mg.
Led
a team that identified the biological compounds in humans
with the highest 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 a versatile cofactor in a variety of physiologic
processes. ApnA molecules function as signal nucleotides
associated with platelet aggregation and neuronal response
and are putative "alarmones" which reportedly
regulate cell proliferation, stress response, and DNA
repair. The findings give indirect evidence that boron
may function in gene expression and blood coagulation.
Representative
Publications:
- Hunt,
CD Dietary boron as a physiological regulator of the
normal inflammatory response: a review and current research
progress. J. Trace Elem. Exp. Med. 12:221-233, 1999.
- Hunt,
C D, Herbel, J L, Nielsen, F H Metabolic response
of postmenopausal women to supplemental dietary boron
and aluminum during usual and low magnesium intake: boron,
calcium, and magnesium absorption and retention and blood
mineral concentrations. Am. J. Clin. Nutr. 65:803-813,
1997
- Hunt,
CD Copper and boron as examples of dietary trace elements
important in bone development and disease. Cur. Opin.
Orthop. 9;V28-36, 1998.
- Hunt,
CD and Idso, JP Moderate copper deprivation during gestation
and lactation affects dentate gyrus and hippocampal maturation
in immature male rats. J. Nutr. 125:2700-2710, 1995
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Adjunct
Professor