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National Institutes of Health (U.S.). Nutrition Co.

Annual report : National Institutes of Health. Program in Biomedical and Behavioral Nutrition Research and Training (Volume 1983) online

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The Division of Research Services (DRS) provides support to the
intramural research efforts of the NIH. Included in these services
is a program in laboratory animal nutrition that routinely provides
investigators with assistance in matters relating to animal diets.
This assistance ranges from providing information regarding the
nutrient concentrations of specific diets to direct collaboration in
studies where dietary nutrients is the major variable and the formu-
lation of special experimental diets is required. The staff of this
program is also involved in monitoring the quality of animal diets
purchased for use throughout the NIH. This is accomplished by rou-
tinely analyzing diet samples for various nutrient and potential
contaminant concentrations.

The laboratory animal nutrition program is responsible for conducting
research with the objective of improving the nutritional status of
animal species used in research and thus improve the overall quality
of animal models. This research has resulted in the development of
an open formula diet for each of the animal species used in signifi-
cant numbers in biomedical research. These open fomiula diets are
not only being used at NIH but also throughout the biomedical re-
search community as standard reference diets. Since the ingredient
composition of open formula diets are readily available, the formula-
tions can be altered to produce diets with either deficient or excess
nutrient concentrations for programs requiring animal models to study
nutrition-rel ated diseases. In addition, open fomiula diets can be
purchased by government agencies via the advertised process. On the
average, a 30 percent savings is realized by using this process as
compared to procuring diets on a sole source basis. The total sav-
ings to NIH research programs resulting from using open formula diets
is approximately $150,000 per year.

Areas of research also conducted by the nutrition program include
identification of the nutrient requiranents of various stocks and
strains of rodents, the characterization of animal models and the
development of diets for animal species being introduced to biomedi-
cal research as new models.



74



NUTRITION RESEARCH TRAINING

The NIH supports training in biomedical and behavioral nutrition research in
both the extramural and the intramural programs. Table IX shows the type and
number of persons trained and the expenditures in FY 1983.

TABLE IX

NIH TRAINING IN NUTRITION, FY 1983















Total Numb(


?r 1






M.D.


Ph.D.


Other




of Persons


FY 1983 1


1 Institute




Degree


Degree


Degree*


Pre-Doc


Trained


Obi igationsi




in thousands!


1 EXTRAMURAL














of dollars) 1


1 Institute Training Grants


7





6


25




INCI




12


577 1


INHLBI




26


59


2


49


136


1002 1


INIDR




1


5


5


1


12


233 1


INIADDK




6


24


1


36


67


690 1


INIAID




6


3








9


9 1


INIGMS




24


1


1


53


79


273 1


INICHD




8


5


2


4


19


268 1


INIA













30


30


4 1


[Subtotal




BT


IM


IT


179


377


3,056 1


1 Individual


Fellowshi


ps


3








4




INHLBI




1


55 1


INIDR







1


1





2


38 1


INIADDK




3


7








10


164 1


INIAID




2











2


18 1


INIGMS




1











1


11 1


INICHD




2


7








9


69 i


INEI




1


1








2


21 1


iNIA







1








1


9 1


IFIC




2





1





3


7 1


1 Subtotal




lY


7U


"2"





M


392 1


1 EXTRAMURAL


SUBTOTAL


95


124


13


179


411


3,448 1


1 INTRAMURAL
















INHLBI




6











6


52 1


INIADDK




5


4








9


311 1


INICHD




IJ^


14


I





32


321 1


1 INTRAMURAL


SUBTOTAL


22


18


7





47


684 1


INIH TRAINING TOTAL


117


142


20


179


458


4,132 1



* other Degree includes M.D./Ph.D, Ph.D./D.D.S. , D.D.S, D.V.M., D.Sc, etc



75



Extramural Trainin g

Within the extramural program, two basic mechanisms are used for
nutrition training support: institutional awards and individual
awards.

The institutional national research service awards, commonly called
"training grants," are designed to enable institutions to make train-
ing awards to individuals selected by them for predoctoral and post-
doctoral research training. In FY 1983, out of the total NIH expen-
diture of $135,152,000 to train 8,963 full-time equivalent persons,
$3,056,000 was expended to train 377 persons in nutrition. Thus,
nutrition training accounted for 2.3 percent of the total NIH train-
ing expenditure and 4.2 percent of the total trainees supported.

The postdoctoral individual national research service awards, called
"fellowships," are awarded to provide postdoctoral research training
to individuals to broaden their scientific background and extend
their potential for research. Out of the total NIH expenditure of
$29,502,000 to support 1,607 fellows in FY 1983, the nutrition pro-
gram expended $391,000 to support 34 fellows. Thus, nutrition fel-
lowships accounted for 1.3 percent of the total NIH expenditure for
fellowships and 2.1 percent of the total NIH supported fellows.

Combining training grants and fellowships, $3,447,000 was expended to
support the 411 persons trained in nutrition in FY 1983. The nutri-
tion expenditure accounted for 2.1 percent of the total NIH training
expenditure and the number of trainees in nutrition accounted for 4.0
percent of the total NIH trainees.

Table X shows that whereas the number of trainees and the financial
support for NIH as a whole remained relatively constant from 1978
through 1983, the number of trainees in the nutrition program doubled
between 1978 and 1979, remained relatively constant until 1982, and
has since increased slowly. As can be seen over the 6-year period,
the number of nutrition trainees reached its highest level yet in FY
1983, with 377 trainees.

Despite the fact that total NIH fellowships have seen a slight in-
crease in FY 1983, the number of nutrition fellowships has continued
to decrease.



76



TABLE X

COMPARISON OF TOTAL NIH AND NUTRITION PROGRAM SUPPORT OF EXTRAMURAL

RESEARCH TRAINING AND FELLOWSHIPS, FY 1978 - FY 1983

(in thousands of dollars)







Total NIH




Nutr


ition


Program I




Training


Fell


owships




Training


Fellowships 1


1 FY


Number
Trainees


of

$


Number
Fellows


of

$


Number
Trainees


Df

$


Number of I
Fellows $ 1


lYear














11978


9,260


117,581


1,863


26,345


130


1,956


39 463 1


11979


9,204


116,193


1,993


27,468


261


2,555


36 466 1


11980


8,878


141,719


1,786


34,669


284


3,201


51 628 1


11981


9,121


144,719


1,574


30,897


268


3,159


36 549 1


11982


8,867


123,407


1,539


27,067


307


2,419


38 415 1


11983


8,963


135,152


1,607


29,502


377


3,056


34 391 1



Examples of areas in which the trainees carried out their work in-
clude the following:

Nutrition and metabolism

Experimental and clinical nutrition

Clinical nutrition for physicians

Graduate training in nutrition

Development of time budgeting, energetic constraints

Role of thermogenesis in body weight regulation

Control of food intake: focus on nutrition and behavior

The influence of gastrointestinal signals on satiety

Nutrition and nephrology

Protein, amino acid, and urea metabolism in humans

Mechanisms of protective effect of dietary protein

Function of protein S, a new vitamin K-dependent protein

Differentiation of proteins in cultured mesothelium

Infectious diseases/basic microbiological mechanisms

Human interferon deficiencies in pediatric patients

Carcinogenesis and drug development

Multidiscipl inary oncobiology

Nutrition and oncology: prevention and intervention

Experimental oncology and nutrition

Sympathetic regulation of fat metabolism during sepsis

Research in burns and trauma

Nutrition metabolism with trauma

Multidiscipl inary heart and vascular disease research



77



Plasma lipoproteins and apoproteins
Nutrition-behavioral cardiovascular disease prevention
Interdisciplinary training program in lung disease
Postdoctoral training in lipid research

Nutrition, lipid metabolism, arteriosclerosis, and atherosclero-
sis
Lipid, lipoproteins, and atherosclerosis
Genetics of atherosclerosis
Characterization of postprandial lipoproteins
Dietary fat in lung microvascular injury from oxygen
Lipoprotein methodology, structure, and function
Chemistry of lipoproteins and atherosclerotic lesions
Cardiovascular epidemiology, biostatistics, and nutrition
Cardiovascular disease prevention
Cardiovascular pathology

Cardiovascular pathophysiology and biochemistry
The role of the liver in cholesterol ester metabolism
Target organ insensitivity to 1,25-(0H) -D,
Metabolism of 1,25-(0H)^-D^ ^

Regulation of 25-(0H) -D^-i-hydroxylase
Vitamin D metabolism during pregnancy and lactation
Intestinal absorption and metabolism of riboflavin
Biotin: the mechanism of carboxyl ation
Maternal nutritional status and plasma volume expansion
Thermal aspects of maternal care in deermice
Nutrition and perinatal biology
Nutrition and growth and development
Training in neonatal biology
Cultural and environmental factors affecting chil d mal nutrition:

Sudest Island Region, New Guinea
Fatty acids as an energy source in pregnancy and in the neonate
The role of biological rhythms in reproductive behaviors, cellu-
lar growth, and differentiation related to the biology of the
neonate
The interrelationships between body metabolism and puberty
Nutrition and oral health

Effect of high levels of fluoride on developing tooth enamel
The role of pigment epithelium in supplying phospholipids or
their precursors, including fatty acids to retinal photoreceptor
cell s
The role of zinc and vitamin A deficiencies independently and
together in the development of the structure and function of
the fetal retina and the level of retinal vitamin A
Vitamin A and epithelium glycoprotein synthesis
Vitamin A status at various gestational ages
Mediation of endotoxin effects on zinc and copper metabolism
Effect of fluoride and calcium++ on amylase secretion

Intramur al Training

Within the NIH intramural program, three Institutes, NHLBI, NIADDK,
and NICHD, supported training of 47 scientists at an obligation of
$684,000 in FY 1983.



78



The intramural trainees worked in the following areas:

Starch metabolism in patients with glycogen storage disease

Basic chemical defect in cystinosis in order to develop new and
improved methods of treatment and diagnosis

Development and evaluation of better means of diagnosis and
treatments for the inborn errors of metabolism

The kinetics of calcium metabolism in normal prepubertal chil-
dren and the evaluation of disease-related changes in calcium
metabolism in both children and adults

Effects of a thiamine deficient diet and ethanol on fetal devel-
opment in an animal model

Role of magnesium in fetal and postnatal maturation, and in the
treatment of infants with apnea

Pathophysiology of fibrodysplasia ossificans progressive and
therapeutic intervention with 13-cis retinoic acid

Nutrition induced alterations in metabolism

Control of macromolecular synthesis during normal growth as well
as nutritional deficiency

Renin-angiotensin system and aldosterone regulation

Biochemical studies of hepatic and intestinal function

The anatomic and physiological causes of the absence of satiety
in Prader-Willi syndrome

Pathophysiology of the adipocyte in human obesity

Effect of overfeeding on glucose disposal

Insulin regulation of glucose transport and metabolism

Hormonal regulation of cellular metabolism in order to define
the defect in glycogen metabolism resulting from diabetes and to
elucidate the mechanism of action of insulin

Diabetes and other chronic diseases in U.S. Indians

Lipoprotein metabolism in Pima Indians

Vitamin D resistance and related disorders.



79



NUTRITION RESEARCH HIGHLIGHTS



The areas of nutrition research presented in this section of the
report reflect those areas where significant advances have been made
over the past year. They include studies on the role of nutrition
in the the early development of the CNS, particularly the brain; the
effects of alcohol consumption on fetal development; the influence
of nutrition on the aging processes; the role of dietary fiber in
health promotion and disease prevention; the development of reliable
methods for the assessment of nutritional status; the etiology,
treatment and prevention of obesity as well as its role as an inde-
pendent risk factor for cardiovascular disease; nutrition and behav-
ior; the relationship of plasma cholesterol levels to the pathogene-
sis of coronary heart disease; the role of nutritional therapy in the
control of diabetes; food allergies; nutrient deficiencies and ex-
cesses found in CNS disorders of amyothrophic lateral sclerosis and
parkinsoni sm-dementia; the role of diet in the development of dental
caries; total parenteral and enteral nutrition; and the effects of
food-borne contaminants and additives on biological systems.

Studies on the role of nutrition in central nervous system develop-
ment includes research on nutrition and early development, particu-
larly brain development. Some studies are examining the hypothesis
that several pathways of brain metabolism in the developing animal
are linked to nutrient availability in the brain. Such studies
attanpt to quantitate developmental changes of both blood-brain
transport and brain metabolism of amino acids. This research will
increase our knowledge as to whether such amino acids as choline,
ornithine, and adenosine are essential to the developing brain and
provide the necessary rationale for monitoring plasma levels of such
nutrients in the fetus.

Additional studies examine undernutrition and its effect on the
plasma membranes of synaptic nerves in the brain. Investigations
have demonstrated that offspring of undernourished rats have a de-
creased concentration of protein and changes in the synthesis of
gang! iosides, glycoproteins, and other specific proteins in the
synaptic plasma membranes. This decrease in protein concentration
may precipitate the synaptic abnormalities observed in these animals.

Other investigations on the effect of diet on brain neurons, particu-
larly the synthesis and release of serotonin by brain neurons have
examined the effects on the sleep patterns of newborn infants of
variations in diet designed to affect tryptophan availability. It is
known that the synthesis and release of serotonin by brain neurons
is proportional to the availability in the brain of its precursor,
tryptophan. The brain tryptophan concentration is influenced by
dietary intake of tryptophan and other large neutral amino acids
(valine, leucine, isoleucine, tyrosine, methionine, and phenylala-
nine) that compete with tryptophan for transport across the blood
brain barrier, as well as the intake of carbohydrate and associated
insulin secretion.



The 20 healthy newborns included in the study were given tryptophan
in a 10 percent glucose solution, or valine in a 5 percent glucose
solution. The tryptophan formula was chosen to maximize the trans-
port of tryptophan across the blood brain barrier, whereas the valine
solution minimized tryptophan transport.

The sleep patterns of the two groups of infants fed tryptophan or
valine were compared to the sleep patterns observed after routine
formula (Similac). The infants fed tryptophan entered active sleep
14.1 minutes sooner than after Similac, and entered quiet sleep 20
minutes sooner. Those infants fed valine entered active sleep 15.8
minutes later than when fed Similac, and entered quiet sleep 39
minutes later.

Data from this research demonstrate that modifications of the prepa-
rations fed to newborns can influence the length of time it takes the
newborn to fall asleep after a feeding. It is believed that the
changes observed in sleep behavior could have been caused by changes
in brain tryptophan and subsequent serotonin synthesis and the neuro-
transmission within the newborn's brain.

Alcohol consumption affects health, and at no other time is the
effect of alcohol consumption more dramatic than during fetal devel-
opment. In order to better understand the effect of alcohol con-
sumption during pregnancy on the proper development of the fetus, an
animal model of pigtailed macaques has been developed to determine
the levels of binge alcohol consumption that can produce defects in
infants of mothers who drink during pregnancy. Early results of
research using this animal model indicate that six cocktails consumed
once a week by the mothers may cause serious problems in newborns.
Once a week, pregnant pigtailed macaques were given either a high
dose of ethanol , equivalent to a binge of 10 cocktails in humans, or
a moderate dose equivalent to 6 cocktails or a 6-pack of beer. The
animals received these doses beginning at 40 days after conception
until the end of term. The animal receiving the high dose of ethanol
produced an infant with facial abnormalities and mental retardation
similar to those seen in human fetal alcohol syndrome (FAS). Of the
three animals receiving the moderate doses of alcohol, one had a
miscarriage, one gave birth to a retarded infant, and one produced
an infant which had signs of FAS.

The study revealed several important similarities of the retarded
animals to children with FAS, i.e., neurological defects were appar-
ent, nerve tissue in the cerebral cortex was inadequately developed,
facial features were adversely affected, and significant changes in
brain receptor activity were observed. The brain of the high dose
infant was small and grossly misshapen, which is also apparent with
human newborns with FAS. This animal was so severely retarded that
it required 5 times as long to develop behavioral patterns normally
observed within 22 days of birth.

Differences between animal and human FAS appeared in weight gain and
skeletal growth. Although human infants with FAS are abnormally
small, the neurological ly retarded monkeys were heavier than average



81



and the male moderate- dose offspring was also taller than normal.
The animals did not have any major mal fonnations in the skeleton,
heart or kidneys, although such malformations occur in human FAS
patients. Even though no particular species can perfectly model the
human, the macaque is preferable to previous FAS models because
primate metabolism and fetal growth patterns are closer to humans
than other mammalian forms. Additional research in this area is
examining the time when drinking during pregnancy causes the most
damage. Studies suggest that brain development can be severely
altered by fetal exposure to alcohol even beyond the first trimester.

Much of the research on nutrition and aging considers whether nutri-
tional needs change significantly beyond the middle decades of life
and, if so, how these needs change and what specific nutrients are
involved. The study of human aging in terms of the genetic and other
environmental factors that influence morbidity and mortality is an
important area of research. Nutrition and diet are certainly among
the most influential environmental factors to exert chronic influence
on the aging organism.

Laboratory and clinical studies are under way to examine the effect
of aging on nutrient requirements, absorption and metabolism, as well
as the effect of diet on the natural history of diseases common in
the elderly such as osteoporosis, diabetes, blindness, cancer, hyper-
tension and atherosclerosis.

A 5-year study of 72 pigtail ed macaques examines the possible inter-
action of nutrition - speci fically , the U.S. diet with its high pro-
portions of fat, cholesterol, simple sugars, and sodium - and normal
biological aging processes that might produce the physiological and
behavioral changes and diseases found in the elderly. One group of
36 monkeys follows the U. S diet while a matched group follows the
alternative diet. The U.S. diet, which is analogous to the one
followed by the average Anerican, has six times the amount of choles-
terol , four times the amount of salt, and twice the amount of sugar
as the "alternative more healthy diet." Neither diet contains alco-
hol, caffeine or common food additives such as preservatives. Each
group of monkeys includes an equal number of males and females rang-
ing in age from 4 to 25 years, a span equivalent to 12 to 75 years
in the human. Animals of various ages and sexes are housed in group
cages to allow for normal social interactions.

Periodic examinations provide information on 48 standard biological
and clinical characteristics and four measures of biological aging.
The studies are designed to clarify the effects of biological aging
and diet on carbohydrate and fat metabolism, psychological functions,
pharmacodynamics, genetic assurance mechanisms, and several specific
disease processes such as periodontal and degenerative bone disor-
ders, atherosclerosis, and preneoplastic mammary dysplasia. Twenty
collaborating investigators across the country are analyzing blood
samples and biopsy specimens in an attempt to clarify the effects of
aging and diet on metabolism, vision, and cell function.



82



This study is designed to answer some of the questions as to how diet
interacts with the biology of aging in the pigtail ed macaque, since
previous studies have identified changes in behavior, mental func-
tion, anatomy and physiology that accompany aging in these animals.
For example, in one 2-year study the oldest animals appeared to have
learning deficiencies, lower levels of certain neurotransmitters in
the brain, thinner capillary walls in the brain cortex, thick coro-
nary vessels, a decrease in the number of alveoli and air space in
the lungs, as well as a decrease in bone mass and menopause. Thus,
this study may identify diet-related problems in these animals that
are similar to problems that occur in man.

A prospective study is under way to examine the nutritional status of
the elderly with investigators analyzing the relationships between
nutrient intakes and their blood levels, and between borderline
deficiencies of specific nutrients and intellectual functioning.
Previous work by investigators has pointed to impaired peripheral
tissue sensitivity to insulin as the primary factor responsible for
the decrease in glucose tolerance observed with advancing age. It is
hypothesized that the abnormal glucose tolerance observed in the
elderly is due to a reduced responsiveness of adipocytes to the
antilipolytic effects of insulin. The theory behind this concept is
that free fatty acids released from adipose tissue or end products of
free fatty acid metabolism inhibit glucose utilization. These inves-
tigators wish to determine if insulin is as effective in the elderly
as in younger controls in reducing the release of free fatty acids
from adipose tissue after a glucose challenge. Various studies are
designed to determine the response of whole body glucose, free fatty
acids and glycerol kinetics to various stimuli, including insulin,
norepinephrine, mild physical exercise, and varying nutritional
status.

Over the past few years, claims have been made that dietary fiber has
a number of beneficial effects on health. The therapeutic effects
include the relief of constipation, the symptomatology of diverticula
disease and the recent indication of its role in controlling glucose
tolerance in diabetics. In addition, the prophylactic effects of
dietary fiber are now being considered, e.g., studies are under way
to closely examine the suggestion of an inverse correlation between
the intake of dietary fiber and the incidence of colon cancer.

In 1977, the NCC held a workshop entitled, "The Role of Dietary Fiber
in Health," to address this issue. A plenary session covered the
state-of-the-art in dietary fiber research; i.e., its historical
aspects, definitions, interactions with bacteria, and its relation to
digestive tract infection and the specific disorders of obesity,
diabetes, cancer and arteriosclerosis. Six working groups covered
such topics as the analysis of the various components of fiber found
in foods; fiber's effects on the function as well as on the develop-
ment of diseases of the gastrointestinal tract; the role of dietary


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Online LibraryNational Institutes of Health (U.S.). Nutrition CoAnnual report : National Institutes of Health. Program in Biomedical and Behavioral Nutrition Research and Training (Volume 1983) → online text (page 10 of 21)