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The Effect of Alpha-Linolenic Acid

on Infant Neuronal Development

Submitted By:
Jane Loprieno

to
William Proulx, PhD, RD
Associate Professor of Nutrition and Dietetics

Dec. 13, 2016

Table of Contents
Introduction.............. 3
Literature Review. 4
A. Impact of Alpha-Linolenic Acid on Problem Solving................. 5
B. Impact of Alpha-Linolenic Acid on Vision............. 6
C. Correlation between Alpha-Linolenic Acid and Attentiveness... 7
D. Impact of Alpha-Linolenic Acid on Learning Ability. 8
E. Impact of Alpha-Linolenic on Motor Skills 9
References.. 10

Introduction
For a growing infant, an ample diet complete with omega 3 fat sources is imperative for
the childs cognitive function. Infants brains are at peak development during the third trimester
and first year of life (8). It is recommended that expecting mothers consume at least 200mg of
DHA during pregnancy and while breast feeding (7). Alpha-linolenic acid (LnA), a precursor of
DHA, contributes to neural development as evidenced by data collected in infant problem
solving skills, vision, attention, learning ability, and motor skills (1, 2, 4, 5, 6). Infants who had
adequate supply of alpha-linolenic acid were more capable of solving problems at a faster rate
than those who did not receive adequate supply (1). These infants also responded to visual
stimuli more accurately (2). Infants are also shown to have a longer attention span and are less
likely to be distracted (4). Through the use of rats, researchers concluded that a diet high alphalinolenic acid results in advanced learning abilities and motor skills (5, 6). This review paper
will analyze various studies that depict the important role alpha-linolenic acid has on neural
development, including problem solving skills, vision, attention, learning abilities, and motor
skills.

Review of Literature
A. Impact of Alpha-Linolenic Acid on Problem Solving
Willatts et al. tested the correlation between polyunsaturated fatty acid supplementation
and infant problem solving (1). Forty-four term infants between 5.5 and 8.8 lbs were given
supplemented formulae with long chain poly unsaturated fatty acids (n=21), or formulae that did
not contain the supplement for four months (n=23). Cognition was assessed using three pretests
and a final complete process test at ten months post-natal. During the pretests infants needed to
remove a barrier to retrieve a toy, remove a cloth to retrieve a toy, and search for a toy after

seeing it hidden under a cloth. They had thirty seconds to complete each pretest. Lastly, the
infants had to complete the three step procedure to retrieve the toy. Infants were analyzed based
on intentional reasoning, rate of problem solving, and attentiveness (p<.05). Infants who
received LCPUFA-supplemented formula had significantly more intentional solutions than
infants who received the no-LCPUFA formula (median 2.0 vs 0, p=0.021). Infants given
supplemented formulas had higher median intentional reasoning scores in comparison to infants
not given supplemented formula (14 vs. 11.5, p=0.035). The infants who were not given
supplemented formulas showed significantly greater distractibility rates, (p<.05), and therefore,
took longer to solve the problem. Multistep processes for problem solving require memory and
attention. Long-chain polyunsaturated fatty acids build up in the cell membrane of the central
nervous system and result in an increased rate of information processing and problem solving.
Due to the attentiveness expressed by the infants who were given supplemented formulas, it was
concluded that long chain fatty acids may support early maturation of the parietal and prefrontal
cortex--areas of the brain that play a role in attentiveness and distractibility.
B. Impact of Alpha-Linolenic Acid on Vision
Makrides et. al determined if it was possible to match bottle fed visually evoked potential
(VEP) and erythrocyte fatty acid profiles to those of breastfed infants by adding a DHA
supplement to the infants formula (2). VEPs are an electrical potential used to indicate
functional integrity of the visual pathway from the retina to the visual cortex of the brain (3). In
order to measure this, the researchers had three groups of healthy, term infants--one breast fed
(n=23), one DHA supplemented formula fed (n=13), and one original formula fed (n=19) (2).
VEP acuity and erythrocyte fatty acid profiles were tested at sixteen (p<.001) and thirty weeks
(p<.01). It was recorded three times at peak amplitude while a high contrast checkerboard screen

played before the infants. Results to these findings indicated that the supplemented formula
group was able to meet the performance of the breast fed group, but not surpass it. The breast
fed and supplemented formula groups results improved over the course of fifteen weeks, while
the original formula group showed a 50% decline and underdeveloped visual acuity. The
researchers stated that their findings correlate to the measured erythrocyte DHA concentration at
post-natal day five and weeks sixteen and thirty which indicates the importance of DHA in the
diet for visual performance. Breastfed and supplemented formula fed infants had significantly
better VEP acuities and erythrocyte fatty acid profiles than the control group at week sixteen
(p<.001) and week thirty (p<.01). Because the brain is still developing in the first year of life,
the researchers concluded that it is best to breast feed the child. However, omega 3 fatty acids
are an essential supplement if the child is formula fed.
C. Correlation between Alpha-Linolenic Acid and Attentiveness
Long chain omega 3 polyunsaturated fatty acids also have an effect on infant attention
(4). Colombo et. al. studied the correlation between intake of alpha-linolenic acid and attention
span. During the third trimester and first year of life, essential fatty acids are passed through the
placenta and then through human milk. Three-hundred and fifty expecting mothers were given
eggs during this time period that were either ordinary eggs or supplemented eggs with 5.35g of
DHA per 100g fatty acid. Infant attentiveness was analyzed at twelve and eighteen months of
age through a single object task and a distractibility assessment (p<.01). During the single object
task, toddlers were given a toy with several buttons and functions for five minutes to understand
and play with as they pleased. Then, the infants were given the toy for three minutes, four
separate times. During the three minute intervals, a seven second segment of a childrens
television program played. Each time the infants were distracted by this program, it was

recorded. Results of this study showed a significant effect of third trimester DHA given to the
mothers (p< .01). Infants whose mothers were not given DHA supplements were five percent
more distracted by the program. They turned 1.75 seconds before the DHA supplemented
infants, and remained looking at the distraction for fifteen seconds longer. Therefore, the
researchers inferred that infants from mothers with higher levels of dietary DHA showed more
mature developmental profiles in regards to attention. While mothers were given the eggs
throughout gestation it was recorded that those with DHA supplemented eggs had, on average, a
six-day longer gestation period and delivered offspring that were longer than those without the
supplemented DHA eggs (50.6cm vs. 49.7cm, p<.05). This can be linked to developmental
attention advantages.
D. Impact of Alpha-Linolenic Acid on Learning Ability
Yamamoto et al. focused on the balance between alpha-linolenic acid (LnA) and alphalinoleate (LA) and the role it has on learning ability (5). This study used three groups of rats to
depict the correlation between long chain polyunsaturated acids and learning ability. For seven
weeks the rats were given specific diets prior to mating, during pregnancy, and during lactation.
After eleven weeks, when the diets were steady, the rats were given a learning test. All three
diets consisted of 39% starch, 25% milk casein, 10% alpha-starch, 8% cellulose powder, 6%
minerals, 5% sucrose, 2% vitamins, and 5% oils which varied among the three groups. The first
groups diet included safflower oil containing .05% LnA and 78.2% LA. The second groups
diet included perilla oil containing 64% LnA and 13% LA. The third group was a control group
consuming a normal diet with 7.7% LnA and 49.5% LA. The learning tests involved dark and
bright lights and the rats understanding of pressing a lever down when the bright light showed.
If the rats did this, they received one pellet. If they pressed the lever while the dark light

showed, they did not. The rats were taught this over three days and then final results were
recorded, which were significantly different between the groups (p<.05). R+ signified a correct
response and R- signified an incorrect response. The average number of days it took for each
group of rats to complete the learning process was recorded (perilla group, 7.7 +/- 2 days vs.
safflower group, 10.8 +/- 2.9 days). At the start of the study, R+ rates of the rats eating a diet
high in LA (group 1) increased rapidly. The R+ responses of the rats consuming a diet high in
LnA (group 2) also increased, but at a slower rate. Group ones R- rates also rapidly increased
while group twos rates gradually decreased throughout the session as the rats learned and
understood. The correct response ratio (sum of R+ and R-) was higher in group two than group
one. The rats consuming a diet deficient in alpha-linolenic acid took far longer to decrease Rrates which indicates that it took longer for these rats to learn and understand the process.
Overall, the researchers concluded that a diet high in alpha-linolenic acid allowed the rats to have
higher R+ rates and fewer R- rates than group one which demonstrates the nutrients positive
effect on learning ability.
E. Impact of Alpha-Linolenic Acid on Motor Skills
Janssen et al. tested the effect of long chain omega 3 polyunsaturated fatty acids on the
cognitive development in mice (6). Omega 3 fatty acids increase membrane fluidity and related
receptor functions that cause improved motor skills. During this study, two groups of mice were
given diets from gestation to post-natal day sixty. Diets were either omega 3 deficient or
adequate to analyze neuronal activity. The adequate diet contained 2.55% alpha-linolenic acid
and 1.28% DHA while the deficient diet contained .05% alpha-linolenic acid and 0% DHA of
total fatty acids. On day thirty and day sixty, the mice were given motor coordination tests in
which they were placed on a rotating rod and required to perform a task. The speed and

acceleration were increased throughout the time in which the mice remained on the disk.
Latency to fall was recorded and compared between both groups. On day thirty, the latent period
of the mice eating a diet adequate in omega 3 was less than that of the omega 3 deficient group
(60 vs. 85 seconds). However, the omega 3 adequate groups latent period increased when
results were recorded on post-natal day sixty (80 seconds). In comparison, the omega 3 deficient
group showed a gradual and consistent decrease in latency to fall from 85 to 60 seconds on postnatal day sixty. The omega 3 adequate fed mice showed a higher latency to fall than the omega
3 deficient mice. The researchers concluded that overall, the group of mice on an omega 3
adequate diet performed significantly better and had more advanced motor skills than the omega
3 deficient group (p<.01). From this study, the researchers concluded that dietary intake of
alpha-linolenic acid during early development has a positive impact on neural development.

Conclusions
Alpha-linolenic acid is necessary for optimal neural development. The brain is at peak
development during the third trimester and first year of life, therefore, adequate supply of this
nutrient is needed at this time. In analyzing infants problem solving skills, Willats et al.
concluded that those who were given supplemented fatty acid formulas performed better than
those consuming regular formulas (1). In regard to vision, Makrides et al. found that infants who
were breast fed had accelerated abilities (2). When researchers tested the vision of infants given
polyunsaturated fat supplements, they were able to match breast fed infant visual abilities. These
long chain fatty acids can also improve attention (4). Colombo et al. showed that infants given
DHA supplements had longer attention spans and were less likely to be distracted. Similarly,
alpha-linolenic acid enhances learning ability (5). Through the use of rats, Yamamoto et al. were
able to identify a positive correlation between polyunsaturated supplementation and advanced

learning. Janssen et al. depicted the accelerated development of motor coordination through the
use of rats when a given diet was adequate in polyunsaturated fats compared to one that was not
(6). The previously reviewed studies demonstrate a common positive correlation between alphalinolenic acid in the diet and neuronal development in regards to problem solving, vision,
attentiveness, learning ability, and motor skills.

References
(1) Willatts, P., Forsynth, J. S., DiModugno, M. K., Varma, S., Colvin, M. (1998) Effect of
long-chain polyunsaturated fatty acids in infant formula on problem solving at 10
months of age. The Lancet, 342 (9129) pp. 688-691.
(2) Makrides, M. PhD., Neumann, M., CMT., Simmer, K., FRACP., Gibson, R., PhD., Pater,
J., FRACO. (1995) Are long-chain polyunsaturated fatty acids essential nutrients
in infancy? The Lancet, 345 (8963), 1463-1468.
(3) Creel, D. J. (2016). Visually Evoked Potentials. Retrieved September 18, 2016, from
http://webvision.med.utah.edu/book/electrophysiology/visually-evokedpotentials/
(4) Colombo, J., Kannass, K. N., Shaddy, D. J., Kundurthi, S., Maikranz, J. M., Anderson, C.
J., Carlson, S. E. (2004). Maternal DHA and the Development of Attention in
Infancy and Toddlerhood. Child Development, 75(4), 1254-1267.
doi:10.1111/j.1467-8624.2004.00737.x
(5) Yamamoto, N., Saitoh, M., Moriuchi, A., Nomura, M., & Okuyama, H. (1987).
Effect of Dietary Alpha-linolenate/linoleate Balance on Brain Lipid
Compositions and Learning Ability of Rats, 28, 144-151. Retrieved
September 20, 2016, from http://www.jlr.org/content/28/2/144.long
(6) Giovannini, M., Riva, E., & Agostoni, C. (1998). The role of dietary polyunsaturated
fatty acids during the first 2 years of life. Early Human Development, 53, 99-107.
doi:10.1016/s0378-3782(98)00068-1
(7) Iranpour, R., Kelishadi, R., Babaie, S., Khosravi-Darani, K., & Farajian, S. (2013).
Comparison of long chain polyunsaturated fatty acid content in human milk in
preterm and term deliveries and its correlation with mothers' diet. Journal Of
Research In Medical Sciences, 18(1), 1-5.

(8) Koletzko, B., Lien, E., Agostoni, C., Bhles, H., Campoy, C., Cetin, I., & ... Uauy, R.
(2008). The roles of long-chain polyunsaturated fatty acids in pregnancy, lactation
and infancy: review of current knowledge and consensus recommendations.
Journal Of Perinatal Medicine, 36(1), 5-14. doi:10.1515/JPM.2008.001
(9) Janssen, C. I., Zerbi, V., Mutsaers, M. P., Jong, B. S., Wiesmann, M., Arnoldussen, I. A.,
Kiliaan, A. J. (2015). Impact of dietary n-3 polyunsaturated fatty acids on
cognition, motor skills and hippocampal neurogenesis in developing C57BL/6J
mice. The Journal of Nutritional Biochemistry, 26(1), 24-35.
doi:10.1016/j.jnutbio.2014.08.002
(0) Willatts, P., & Forsyth, J. (2000). The role of long-chain polyunsaturated fatty acids in
infant cognitive development. Prostaglandins, Leukotrienes and Essential Fatty
Acids (PLEFA), 63(1-2), 95-100. doi:10.1054/plef.2000.0198

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