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ESSENTIAL FATTY ACIDS AND INFANT NUTRITION
Borden Award Address
By Arild E. Hansen, M.D., Ph.D.Department of Pediatrics, University of Texas School of Medicine
494
PEDIAmIcs, March 1958
ARILD EDSTEN HANSEN was born in Minne-
apolis during the last year of the last centuryand grew up in that city. He was educated inthe schools of Minneapolis and at the Univer-sity of Minnesota where he received his de-grees: B.S. in 1923, M.B. in 1924, M.D. in
1925 and Ph.D. in 1934. Arild Hansen alsospent the years 1929 and 1930 in post-gradu-
ate studies at Heidelberg and Vienna. He
served the University of Minnesota as an As-
sistant and an Instructor of Pediatrics until
1934. The year 1934-35 was spent as anAlexander Brown Coxe Fellow at Yale Uni-versity. Upon returning to Minnesota, Dr.
Hansen became Assistant Professor of Pedi-atrics, in 1937 Associate Professor and in 1942
Professor. In 1944 Dr. Hansen traveled fromthe extreme north to the extreme south of the
United States to become Professor of Pediatricsand Head of the Department at the Universityof Texas Medical Branch in Galveston. Dr.
Hansen is a member of numerous scientificsocieties. He has a long career in investigation
and published many articles on a variety of
topics but especially on lipid metabolism.
T N A PRESENTATION such as this, no doubt,I one is allowed the equivalent of a cer-
tam degree of “poetic license” in reviewing
the work which has led to commendation
by the Committee on Awards of the Amen-
can Academy of Pediatrics. Collaboration
is not only an essential feature of present-
day investigative endeavors, but also a so-
cial reward. As with everyone else, per-
haps, who has attempted to pursue “ideas,”
the writer has found persons who stand out
as vital and indispensable in seeking to
establish fantasy or fact in relation to con-
cepts conceived. In regard to the subject
of the essential fatty ‘acids, it has been my
Presented at the Annual Meeting, October 8, 1957.ADDRESS: Galveston, Texas.
pleasure and privilege to work in the most
stimulating manner with the late William
R. Brown, Mildred R. Ziegler, George 0.
Burr, Irvine McQuarrie, William R. Wilson
and in recent studies for which this award
is being given with Doris J. D. Adam, and
especially with Hilda F. Wiese of the Uni-
versity of Texas School of Medicine.
Each of us can recall events from our
school years which have harried us long
after their direct relationship to the subject
has been forgotten. A statement during my
premedical days, which for some reason or
other stuck as “gum to a shoe,” was made
by Professor Lee I. Smith of the Depart-
ment of Organic Chemistry while dis-
cussing the subject of fat. After mentioning
that the fatty acids found in nature have
an even number of carbon atoms, he added,
“there are some which have unsaturated
linkages, but no one knows the reason for
this.” I still recall placing a question mark
in my notebook to indicate “I wonder why.”
EARLY CLINICAL AND CHEMICALOBSERVATIONS
It was purely a clinical impression some
years later,� which stimulated my interest
in the significance of dietary fat, particu-
lan!>’ in regard to the essential nature of cer-
tam unsaturated fatty acids in human nu-
tnition. In caring for the infant with eczema,
it was the general therapeutic practice to
remove fat from the diet. During my hos-
pital-training years, as well as in private
practice, I followed this procedure; how-
ever, the results were unimpressive. Still,
the problem of eczema seemed to offer a
challenge, especially after I had visited a
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TABLE II
LIPID IN SERUM IN RATS AND Doos
AMERICAN ACADEMY OF PEDIATRICS-PROCEEDINGS 495
number of the Children’s Hospitals of
Europe and noted the uniformity of the
problem, i.e., similarity of manifestations
and difficulty in management.
It was about this time that Burr and
Burr2 had published their astute observa-
tions on the effects of fat-free diets on rats.
The idea that lack of dietary fat could pro-
duce profound changes in the appearance
of the skin, which were cured by the addi-
tion of special fats to the diet, was an allur-
ing idea. After some deliberation, this new
approach to the problem of eczema was
tried. A number of infants suffering with
eczematous eruptions were given supple-
ments of fats, such as fresh lard, corn oil
or raw linseed oil, which contain unsatu-
rated fatty acids. In none did the eruption
become worse; whereas, after several weeks
some infants appeared to be definitely im-
proved.
It was these clinical observations which
led me to the laboratory to learn something
about lipid analysis in order to study blood
fats. It was found that the iodine numbers
of the fatty acids of the serum of infants
with eczema were lower than those of in-
fants free from such skin 3 In our
initial studies it was found that with no
essential difference in the concentration of
the total fatty acids of the serum, the iodine
number of the fatty acids was 84 on the
average in the infants with eczema com-
pared with 111 in control infants (Table I).
Following the administration of dietary fats
which contained unsaturated fatty acids,
TABLE I
LIPID IN SERUM IN INFANTS WITH
ECZEMA AND IN CONTROLS
Total Fatty Acid.�
(mg/100 ml) (mean iodine no.)
Control’ 361 111
Eczema’ 34� 84
Control’ 339.4± 6.� 11�.O±3.7
Eczema3 387.3± 1�L5 87.O±�.�
Total F aLly Acid.�
(mg/100 ml) (mean iodine no.)
Rats5
Control diet �8S 136
Low-fat diet �58 107
Dogs7
Control diet 53� 117
Low-fat diet 455 9�
the iodine values of the serum fatty acids
were found to be in the same range as for
the control subjects.4 The changes in iodine
number of the fatty acids frequently coin-
cided with clinical improvement. After dis-
cussing these observations with Dr. Mc-
Q uarnie he suggested that I see Dr. Burr
who was a member of the Department of
Botany in the same institution. From him
it was learned that no studies of the serum
fatty acids in rats had been made, but he
agreed that such a project was worthy of
pursuit.
Arrangements were made to analyze the
serum lipids of fat-deficient and control
6 The results showed that the differ-
ence in iodine numbers of the serum fatty
acids between animals suffering from fat
deficiency and healthy control animals was
of the same order of magnitude as was ob-
served between eczematous and control in-
fants. As indicated in Table II, subse-
quently this also was found to hold for
dogs.7 These preliminary observations mdi-
cated that a thorough study of blood lipids
in relation to dietary fat might be helpful
in evaluating the role of fat in the mainte-
nance of healthy skin. However, to conduct
such a study two features were apparent:
Firstly, a method for the determination of
specific fatty acids in blood serum would
assist materially in carrying out such a
project; secondly, actual experience with
low-fat diets would be necessary to estab-
lish an essential role of fatty acids in hu-
man nutrition.
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FIG. 1. Young dogs of same age since weaning (a, left) fed on diet in which fat (fresh lard) comprised
29% of the calories and (b, right) same diet except sucrose substituted for fat (total tat 1% of total
caloric intake).
496 ESSENTIAL FATTY ACIDS
DEVELOPMENT OF METHODS FORLIPID ANALYSIS AND THEIR
APPLICATION
The first step in the development of
methods was a semimicrogravimetric pro-
cedure for the direct determination of fat
by Wilson and Hansen,8 wherein it was
possible to separate the fatty acids from
the unsaponifiable fraction. Further frac-
tionation allowed one to determine the
amount and average degree of unsaturation
of the fatty acids present as phospholipids.�
Subsequently, by means of alkaline conju-
gation of unsaturated fatty acids and spec-
trographic analysis by the method of Wiese
and Hansen,1#{176} it was possible to measure
the amount of the 2-, 3- and 4-double-bond
fatty acids in blood serum and body tissues.
Next, in order to establish correlations
between dietary fat and clinical appearance
of the skin, as well as between dietary fat
and concentration of specffic fatty acids in
the serum, an extensive series of expeni-
ments were carried out with young pup-
pies.1114 Incidentally, our first efforts at
feeding a diet extremely low in fat to dogs
resulted in vitamin E deficiency, which
was evidenced by the development of
paralysis of the hind extremities. Recovery
occurred with the addition of alpha-
tocopherol to the diet, but not by the addi-
tion of fat.
To date, well over 100 dogs have been
studied, some of which have been under
observation for as long as 6 years. These
studies established the following facts:
1. Signs of fat deficiency readily develop
in young puppies. These are characterized
by dryness of the skin and loss of hair, des-
quamation, erythema and pigmentation of
the skin, running of the ears, oozing of the
paws and a tremulous, nervous behavior.
Some of these signs are not unlike those
observed in some infants who have been on
diets very low in fat. The rate at which the
symptoms of deficiency in dogs disappear
is directly related to the quantity of linoleic
acid in the diet. Examples of control and
fat-deficient dogs are shown in Figure 1.
Adult dogs did not show the severe signs
of deficiency which were observed in young
animals. In spite of a caloric intake per
unit body weight equal to that of control
animals, marked emaciation ultimately de-
velops in young animals which do not re-
ceive fat in the diet.
2. Histologic examination reveals marked
alterations in the structure of the skin of
fat-deficient animals. There is parakeratosis
with peeling of the outer layers and pres-
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-. ‘.‘ �__..�,‘l�’z
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AMERICAN ACADE�lY OF PEDIATRICS-PROCEEDINGS 497
FIG. 2. Histologic appearance of skin from (a, left) healthy control dog receiving fat in the diet and
(h, right) animal on diet low in fat.
ence of nucleated cells in the stratum cor-
neum, an increase in the cell layers of the
epidermis and hair follicles, plugging of the
hair follicles, increased activity in the Se-
baceous glands and later signs of atrophy,
evidence of activity of sudoriparous glands,
infiltration of the dermis and uneven col-
lagen fibers. Examples of the skin changes
in control and fat-deficient animals are
shown in Figure 2. The rate at which the
abnormal histologic structures disappear is
related to the linoleic acid content of the
dietary fat.
3. Although the iodine number of the
serum fatty acids of dogs decreases with
a low-fat diet as indicated in Table II,
greater significance is assigned to the direct
correlation between dienoic (linoleic) acid
content of the serum and the linoleic acid
content of the diet. The concentration of
tetraenoic (arachidonic) acid in the serum
changes in the same direction as that of
dienoic acid, whereas the change for tn-
enoic acid is in the opposite direction (Table
III). The increase in trienoic acid in fat-
deficient animals is a subject of considera-
ble interest to a number of workers in this
field.
It was concluded from the studies with
dogs that: Young subjects appear to be
much more sensitive to a lack of fat in the
diet than adults; dermal structures are af-
fected particularly; metabolic processes
concerned with utilization of calories are
altered; and measurement of the di-, tn-
and tetraenoic acids of the blood serum
(2-, 3- and 4-double-bond fatty acids) might
well give one an index for determining the
requirement for unsaturated fatty acids in
the diet of infants.
ATTEMPT TO ESTABLISH THE INFANT’SREQUIREMENT FOR UNSATURATED
FATtY ACIDS
Clinical Observations on Human Subjects
Maintained on Diets Low in Fat
During the first short-term studies of in-
fants given diets low in fat, it was observed
that impetiginous skin eruptions were diffi-
cult to heal. One infant with chylous
TABLE Ill
UNSATURATED FATTY ACIDS IN SERUM OF D0GS’#{176}
‘ Total � Dienoic Trienoic Tetra-
. P.4. � enouI)�et
(mgi
� 1(X) ml) � (per cent of TFA)
Low-fat � 367 5.’2 15.9 3.5
Fat (lard) 30%
of calories 479 �2�t .7 1 . ‘2 ‘21 .1
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498 ESSENTIAL FATTY ACIDS
ascites,15 who for almost 2 years was given
a diet very low in fat, showed: (1) Normal
increase in height (not possible to evaluate
weight curve); (2) food consumption greater
than expected; (3) evidences of disturbed
skin function as indicated from develop-
ment of a chronic dermatitis following
prickly heat, periodic eczematous lesions
and resistance to treatment of impetigo.
An adult subject’6 for a 6-month period
was maintained on a diet low in fat (com-
posed of skimmed milk, cane sugar, potato
starch, baking powder, sodium chloride,
orange juice, ferric chloride, Viosterol#{174}, and
carotene, with liquid petrolatum incorpo-
rated as a shortening in the attempt to make
something equivalent to biscuits); the total
fat intake was not more than 2 gm per day.
Rats maintained on the same diet devel-
oped typical signs of fat deficiency. The
adult subject maintained a state of well
being during the 6-month period. At the
beginning of the study the blood pressure
bordered on the hypertensive level, but
while on the low-fat diet was within the
normal range. During this time he did not
suffer headaches to which he had been sub-
ject periodically. He lost 14 pounds in weight
in spite of a caloric intake and degree of
physical activity similar to that to which he
was accustomed both before and after the
special-diet period. Determinations of the
respiratory quotient indicated that the hu-
man subject reacted metabolically similar
to the rat.
These observations of an infant with
chylous ascites and of an adult subject are
presented in some detail because of subse-
quent findings in two large groups of in-
fants. In a study of 20 infants under 1 year
of age, fed diets containing variable
amounts of fat and linoleic acid, it was ob-
served on several occasions that use of a
low-fat diet was associated with changes in
the skin. In another more extensive study
which is now underway, it has been demon-
strated that linoleic acid plays a definite
role in the maintenance of healthy skin in
young babies.
Chemical Observations on Serum Lipids
With a diet low in fat, in human subjects,
the iodine number of the serum fatty acids
decreases. More significant, however, seems
to be the observationl7 that the 2- and 4-
double-bond fatty acids decrease while the
3-double-bond fatty acids increase. Al-
though the values for the unsaturated fatty
acids in human subjects and dogs are dif-
ferent, the change is in the same direction
as has been noted for dogs.18 This phase
of our studies will be discussed in greater
detail in subsequent reports.
Caloric Consumption in Relation to
Linoleic Acid Intake
Although studies relating the caloric in-
take to linoleic acid in the diet have been
completed, only preliminary reports19 have
been presented. We are desirous of ac-
knowledging the valuable assistance in
these studies provided by a contract from
the United States Department of Agnicul-
ture, Human Nutrition Research Division.
The study was undertaken primarily to as-
certain whether or not one could determine
the infant’s requirement for linoleic acid
by using the concentrations of di-, tn- and
tetraenoic acids in the serum as an index
of adequacy of intake. Milk mixtures were
fed which varied in contents of fat as well
as linoleic acid. Close relationships were
found between the concentration of the
unsaturated fatty acids in the serum and the
linoleic acid intake (Table IV).
In addition, careful clinical observations
and ordinary laboratory studies were made
and accurate records of the food intake
were kept. When the caloric intakes and
the body weights were fitted to straight
lines, it was found that the caloric intake
varied with the linoleic acid content of the
milk mixture. The data from a male infant
who was 2 weeks of age at the beginning of
the study are presented graphically in Fig-
ure 3. One may note no essential change in
the slope of the weight curve whether the
infant received the skimmed-milk prepara-
tion (contained 1% of the calories as fat,
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4.1
3.8
(-DIET A (SKIM MILK)-)�----- -DIET B (EVAP. M1LK)-�
WEIGHT GAIN 25 am P11 DAY WEIGHT GMN 27 am P11 DAY
3.5
3.2
2.9
2.3
02 8 14 20 26 32 38 44 50 56
AMERICAN ACADEMY OF PEDIATRICS-PROCEEDINGS 499
TABLE IV
LIPID IN SERUM PROM INFANTS CONSUMING Mn.xs on VARIABLE CONTENT OF
FAT AND LIN0riac AciD
Diet No. of InfantsTotal F.A.
(mg/100 ml)
Dienoic Trienoic Tel raenoic
(per cent of TFA)
Low-fat 3 .5.� 4.8
Evaporatedmilk 4 10.4 3.4 5.�Breastmilk 4 �67 �13.1 0.4 10.6
0.04% of the calories as linoleic acid) or the
evaporated-milk mixture (contained 40% of
the calories as fat, 1% of the calories as
linoleic acid). Both preparations contained
20 calories per ounce.
At the beginning of the study this infant
was consuming food at the rate of about
110 cal/kg/day. After 4 weeks this had
increased to about 160 cal/kg/day. As soon
as fat was added to the diet, in an evapo-
rated-milk formula, a definite decrease in
2.6
the calories consumed per unit body weight
occurred, so that after 4 weeks he was con-
suming food at the rate of about 100 cal/
kg/day. The average gains in weight were
25 and 27 gm/day on the skimmed-milk
and evaporated-milk mixtures, respectively.
In the final report of the study, data will
be presented which indicate that a similar
decrease in calories consumed per kilogram
per day occurred when the skimmed-milk
mixture was supplemented with small
�Ys
C)
P1
Cl)
I
Fic. 3. Data from an infant who was fed a skimmed-milk mixture from 2 to 6 weeks of age and an
evaporated-milk mixture from 6 to 10 weeks of age.
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500 ESSENTIAL FATTY ACIDS
amounts of linoleic acid. It appears that
linoleic acid plays a signfficant metabolic
role in infant nutrition. This tentative con-
clusion is based on incomplete evaluation
of data obtained from study of 20 different
infants.20
Finally, it may be of interest to note that
the presentation of the Borden Award on
behalf of the American Academy of Pe-
diatrics for 1957 is being made to one who
comes from the same town (Galveston)
where Gail Borden carried on his work
which led to his epoch-making discovery.
The one hundredth anniversary of his com-
pany is now being celebrated. Just last
week I visited his homesite, read some of
his original communications in our city
(Rosenberg) library, and was again im-
pressed with the extraordinary versatility
and accomplishments of this unusual man.
He lived in Galveston from 1837-1851 and
returned there just a century ago to join
his family before going on to seek further
financial assistance to put his discovery of
a process for evaporating milk to use. It
was in Galveston in 1840 that Gail Borden,
J r. made his basic observations regarding
the evaporation of milk under vacuum to
produce a product which would stay clean
for long periods. It is noteworthy that he
did not undertake his investigative efforts
strenuously until he was approaching 50
years of age. Among his accomplishments
we find that as a surveyor he compiled the
first topographical map of Texas and laid
out the City of Galveston. He published the
first newspaper in Texas (Telegraph and
Texas Register) in which was first printed
the Declaration of Independence of Texas
(1835) as well as its Constitution which
he helped to write. He was the first collec-
ton of customs and helped to organize the
First Baptist Church in Galveston (his
mother was a great, great granddaughter
of Roger Williams). He was a close friend,
counsellor and collaborator of the great
leaders and patriots of Texas, Stephen F.
Austin and Sam Houston. After diligent
endeavors he invented a meat biscuit which
received acclaim, but failed to impress the
food buyers for the army, yet orders from
England indicated that his product was
sent to Florence Nightingale to help her
in her plight during the Crimean War. Mr.
Borden went to England where he received
The Great Counsel Medal at the London
International Exposition. Upon returning to
Galveston in 1851 the cows on board ship
became ill, and he observed that the infants
on ship also became ill and some died.
Apparently, it was this experience which
spurred him on to work upon his idea of
milk processing to produce a clean milk.
He believed in cleanness of milk long before
the concept of microbes had been intro-
duced. What he learned in pursuing the
idea of making a desiccated meatball or
meat biscuit and the accidental discovery
of a method for keeping milk clean and
safe has been the turning point in the lives
of many men.
Let this be an inspiration to us all, old
and young, in medicine and science: Casual
observations, if carefully made, often prove
to be more than incidental in importance!
REFERENCES
1. Hansen, A. E. : Study of iodine number ofserum fatty acids in infantile eczema.Proc. Soc. Exper. Biol. & Med., 30:1198,1933.
2. Burr, G. 0., and Burr, M. M. : A new de-ficiency disease produced by the rigidexclusion of fat from the diet. J. Biol.
Chem., 82:345, 1929.3. Hansen, A. E. : Serum lipids in eczema
and in other pathologic conditions. Am.J. Dis. Child., 53:933, 1937.
4. Hansen, A. E. : Serum lipid changes andtherapeutic effects of various oils in in-fantile eczema. Proc. Soc. Exper. Biol.
& Med., 31:160, 1933.5. Hansen, A. E., and Burr, G. 0. : Iodine
numbers of serum lipids in rats fed onfat-free diets. Proc. Soc. Exper. Biol. &Med., 30:1201, 1933.
6. Hansen, A. E., and Brown, W. R. : Theeffect of low fat diets on serum lipidsof rats. J. Nutrition, 13:351, 1937.
7. Hansen, A. E., and Wiese, H. F. : Studieswith dogs maintained on diets low infat. Proc. Soc. Exper. Biol. & Med., 52:205, 1943.
8. Wilson, W. R., and Hansen, A. E. : Study
of the serum lipids by a microgravimet-
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AMERICAN ACADEMY OF PEDIATRICS-PROCEEDINGS 501
nc technique. J. Biol. Chem. 112:457,1936.
9. Hansen, A. E. : Nature of fatty acids of
acetone insoluble (phospholipid) fractionof serum. Proc. Soc. Exper. Biol. & Med.,40:376, 1939.
10. Wiese, H. F., and Hansen, A. E. : Semi-micromethod for unsaturated fatty acids
of blood serum. J. Biol. Chem., 202:417,1953.
11. Hansen, A. E., and Wiese, H. F. : Fat inthe diet in relation to nutrition of thedog. I. Characteristic appearance andgross changes of animals fed diets withand without fat. Texas Rep. Biol. &Med., 9:491, 1951.
12. Wiese, H. F., and Hansen, A. E. : Fat inthe diet in relation to nutrition of thedog. II. Lipid composition of tissuesfrom animals fed diets with and withoutfat. Texas Rep. Biol. & Med., 9:516,1951.
13. Wiese, H. F., and Hansen, A. E. : Fat inthe diet in relation to nutrition of thedog. III. Spectral analysis for unsatu-rated fatty acid content of tissues fromanimals fed diets with and without fat.Texas Rep. Biol. & Med., 9:545, 1951.
14. Hansen, A. E., Holmes, S. G., and Wiese,H. F. : Fat in the diet in relation to nu-trition of the dog. N. Histologic fea-
tures of skin from animals fed dietswith and without fat. Texas Rep. Biol.& Med., 9:555, 1951.
15. Hansen, A. E., and Wiese, H. F. : Tissuelipids in child with chylous ascites main-tamed on low fat diet. Fed. Proc., 5:233,1946.
16. Brown, W. R., Hansen, A. E., Burr, C. 0.,and McQuarnie, I. : Effects of prolongeduse of extremely low-fat diet on an adulthuman subject. J. Nutrition, 16:511,1938.
17. Wiese, H. F., Hansen, A. E., Adam, D.
J. D., and Baughan, M. A. : Effect ofintake of linoleic acid on unsaturatedfatty acids of serum of infants. Fed.Proc., 15:577, 1956.
18. Wiese, H. F., Baughan, M. A., and Han-sen, A. E. : Influence of fat in diet ondistribution of unsaturated fatty acids inserum of dogs. Fed. Proc., 14:453, 1955.
19. Hansen, A. E., Wiese, H. F., Lawlis, M.,Adam, D. J. D., and Baughan, M. A.:Effect of dietary fat on unsaturated fattyacids of serum of infants. Fed. Proc.,14:436, 1955.
20. Hansen, A. E., et al.: Intake of linoleicacid in relation to serum unsaturatedfatty acids and fat deficiency symptomsin infants (abstract). A.M.A. J. Dis.Child., 94:398, 1957.
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1958;21;494Pediatrics Arild E. Hansen
ESSENTIAL FATTY ACIDS AND INFANT NUTRITION: Borden Award Address
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ESSENTIAL FATTY ACIDS AND INFANT NUTRITION: Borden Award Address
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