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Essential fatty acids and human brain



The human brain is nearly 60 percent fat. We've learned in recent years that fatty acids are among the most crucial molecules that determine your brain's integrity and ability to perform. Essential fatty acids (EFAs) are required for maintenance of optimal health but they can not synthesized by the body and must be obtained from dietary sources. Clinical observation studies has related imbalance dietary intake of fatty acids to impaired brain performance and diseases. Most of the brain growth is completed by 5-6 years of age. The EFAs, particularly the omega-3 fatty acids, are important for brain development during both the fetal and postnatal period. Dietary decosahexaenoic acid (DHA) is needed for the optimum functional maturation of the retina and visual cortex, with visual acuity and mental development seemingly improved by extra DHA. Beyond their important role in building the brain structure, EFAs, as messengers, are involved in the synthesis and functions of brain neurotransmitters, and in the molecules of the immune system. Neuronal membranes contain phospholipid pools that are the reservoirs for the synthesis of specific lipid messengers on neuronal stimulation or injury. These messengers in turn participate in signaling cascades that can either promote neuronal injury or neuroprotection. The goal of this review is to give a new understanding of how EFAs determine our brain's integrity and performance, and to recall the neuropsychiatric disorders that may be influenced by them. As we further unlock the mystery of how fatty acids affect the brain and better understand the brain's critical dependence on specific EFAs, correct intake of the appropriate diet or supplements becomes one of the tasks we undertake in pursuit of optimal wellness.
From the 1Department of Neurology, Chi-Mei Medical Center,
Tainan, Taiwan; 2Institute of Biotechnology, College of
Engineering, Southern Taiwan University, Tainan, Taiwan;
3Department of Anesthesia, Chi-Mei Medical Center, Tainan,
Received July 1, 2009. Revised August 17, 2009.
Accepted September 11, 2009.
Reprint requests and correspondence to: Chia-Yu Chang, MD.
Department of Neurology, Chi-Mei Medical Center, No. 901,
Chung Hwa Road, Yung Kang City, Tainan County 710,
Acta Neurologica Taiwanica Vol 18 No 4 December 2009
Essential Fatty Acids and Human Brain
Chia-Yu Chang1,2, Der-Shin Ke1, and Jen-Yin Chen3
Abstract- The human brain is nearly 60 percent fat. We’ve learned in recent years that fatty acids are
among the most crucial molecules that determine your brain’s integrity and ability to perform. Essential
fatty acids (EFAs) are required for maintenance of optimal health but they can not synthesized by the body
and must be obtained from dietary sources. Clinical observation studies has related imbalance dietary intake
of fatty acids to impaired brain performance and diseases.
Most of the brain growth is completed by 5-6 years of age. The EFAs, particularly the omega-3 fatty
acids, are important for brain development during both the fetal and postnatal period. Dietary decosa-
hexaenoic acid (DHA) is needed for the optimum functional maturation of the retina and visual cortex, with
visual acuity and mental development seemingly improved by extra DHA. Beyond their important role in
building the brain structure, EFAs, as messengers, are involved in the synthesis and functions of brain neu-
rotransmitters, and in the molecules of the immune system. Neuronal membranes contain phospholipid
pools that are the reservoirs for the synthesis of specific lipid messengers on neuronal stimulation or injury.
These messengers in turn participate in signaling cascades that can either promote neuronal injury or neuro-
The goal of this review is to give a new understanding of how EFAs determine our brain’s integrity and
performance, and to recall the neuropsychiatric disorders that may be influenced by them. As we further
unlock the mystery of how fatty acids affect the brain and better understand the brain’s critical dependence
on specific EFAs, correct intake of the appropriate diet or supplements becomes one of the tasks we under-
take in pursuit of optimal wellness.
Key Words: Essential fatty acids, Human brain, Omega-3 fatty acids
Acta Neurol Taiwan 2009;18:231-241
The human brain is nearly 60 percent fat. Doctors
probably ignored this fact because they thought dietary
fat had little influence on the brain. Today we know dif-
ferently. We’ve learned in recent years that fatty acids
are among the most crucial molecules that determine
your brain’s integrity and ability to perform.
Review Article
Acta Neurologica Taiwanica Vol 18 No 4 December 2009
Essential fatty acids (EFAs) are required for mainte-
nance of optimal health but they can not synthesized by
the body and must be obtained from dietary sources.
They are also called polyunsaturated fatty acids
(PUFAs). There are two classes of PUFAs--omega-6 and
omega-3. The parent omega-6 fatty acid, linoleic acid
(LA) is desaturated in the body to form arachidonic acid
while parent omega-3 fatty acid alpha-linolenic acid
(ALA) is desaturated by microsomal enzyme system
through a series of metabolic steps to form eicosapen-
taenoic acid (EPA) and decosahexaenoic acid (DHA)(1).
Some of these long-chain metabolites form precursors to
respective prostaglandins, thromboxanes, leukotrienes,
and prostacyclin, which have a tremendous effect on the
brain’s blood flow, immune system and the neurotrans-
mitter system(2) (Fig.).
Among the significant components of cell mem-
branes are the phospholipids that contain fatty acids
(FAs). The types of FAs in the diet determine the types
of FAs that are available to the composition of the cell
membranes. A phospholipid made from a saturated fat
has a different structure and is less fluid than one that
incorporates an EFA. In addition, LA and ALA per se
have an effect on the neuronal membrane fluidity. They
are able to decrease the cholesterol level in the neuronal
membrane, which would otherwise decrease membrane
fluidity, which in turn would make it difficult for the cell
to carry out its normal functions and increase the cell’s
susceptibility to injury and death(3). These consequences
for cell function are not restricted to absolute levels of
EFAs alone, rather it appears that the relative amounts of
omega-3 FAs and omega-6 FAs in the cell membranes
are responsible for affecting cellular function and subse-
quently promoting the pathogenesis of many chronic dis-
eases, including cardiovascular disease, cancer, osteo-
porosis, and inflammatory and autoimmune diseases(4).
Very high levels of FAs and lipids can be found in
two structural components: the neuronal membrane and
the myelin sheath. About 50% of the neuronal membrane
is composed of FAs, while in the myelin sheath lipids
constitute about 70%. The lipid component has a rela-
tively high turnover rate, in contrast to the protein com-
ponent that is especially stable(5). The integrity of the
myelin is of utmost importance for the proper functions
of axons in the nervous system. Breakage or lesions in
the myelin can lead to disintegration of many of the ner-
vous system functions. Recent studies emphasize the
major role of dietary EFA to the normal functions of
Metabolic pathway for essential
fatty acids.
GLA: gamma linolenic acid; PGs:
prostaglandins; TXs: thromboxanes;
LTs: leukotrienes.
oil of corn,
oils of
cold water
Acta Neurologica Taiwanica Vol 18 No 4 December 2009
myelin. Moreover, the EFAs are important in the active
phase of the myelin synthesis. If EFAs are not available
in this phase or are metabolically blocked, amyelination,
dysmyelination, or demyelanation may occur(6). If EFA
deficiency occurs during the postnatal period, a major
delay in the myelination process will occur, accompanied
by impaired learning, motor, vision, and auditory abnor-
malities(7). The goal of this review is to give a new under-
standing of how EFAs determine our brain’s integrity and
performance, and to recall the clinical conditions of the
brain that may be influenced by them.
The main dietary sources of omega-6 FAs are veg-
etable oils like sunflower oil, safflower oil, sesame oil,
and corn oil. The rich dietary sources of omega-3 FAs
are vegetable oils like flaxseed or canola oil, peanut oil,
walnut oil, green leafy vegetables, oily cold-water fish
(mackerel, sardine, and salmon etc.) and fish oil. It is
from these EFAs that our bodies make the vital brain-fats
and the vital messengers that help regulate a vast array of
body activity. Without the EFAs, our bodies run out of
the building blocks our cells require to maintain peak
function(8). Returning to the dietary trends of humans,
we’ll recall that ancient diets contained a ratio of omega-
6 to omega-3 FAs estimated to be roughly 1:1. Today the
ratio is more on the order of 15:1-17:1(4) In addition, to
such “acquired” dietary imbalances that lessen omega-3
intakes, the healthy human organism has limited capacity
to elaborate the long chain DHA and EPA from shorter-
chain precursors. Metabolic biochemists have calculated
that five percent or less of dietary ALA is converted to
EPA, and less than 0.5 percent of dietary ALA makes it
to DHA(9). This change ratio of FAs appears to have sig-
nificant implications for brain function. When scientists
studied the brain of people with multiple sclerosis, they
found that the brain tissue was very low in important
fatty acids such as DHA(10). They also found low levels of
omega-3 FAs in blood and almost no omega-3 FAs
stored in fat tissues. Doctors in Australia who studied the
blood of people with moderate to severe depression
found the balance of EFAs was significantly altered; the
level of the omega-3 FAs was too low(11). Researchers of
Purdue University found that individuals with symptoms
of hyperactivity and attention deficit had lower levels of
the omega-3 FA and DHA in their blood(12). All these
clinical observation studies related imbalance dietary
intake of FAs to impaired brain performance and dis-
eases in some genetic vulnerable individuals.
EFAs and brain development
Most of the brain growth is completed by 5-6 years
of age. At birth brain weight is 70% of an adult, 15%
brain growth occurs during infancy and remaining brain
growth is completed during preschool years(13). The
EFAs, particularly the omega-3 FAs, are important for
brain development during both the fetal and postnatal
period. Both omega-3 and omega-6 FAs play important
roles in neuronal growth, development of synaptic pro-
cessing of neural cell interaction, and expression of
genes regulating cell differentiation and growth. Dietary
DHA is needed for the optimum functional maturation of
the retina and visual cortex, with visual acuity and men-
tal development seemingly improved by extra DHA(14). In
addition, the fetus and placenta are dependent on mater-
nal EFA supply for their growth and development, with
DHA-supplemented infants showing significantly
greater mental and psychomotor development scores and
breast-fed children do even better(15). Reduced DHA is
also associated with impairments in cognitive and behav-
ioral performance, which are particularly important dur-
ing brain development(16). From above findings we may
suggest that providing proper FA balance during the
infant period increases the opportunity to ensure that any
child can realize his or her peak potential. It also raises
the possibility that a child suffering from learning,
behavior, or other brain-related problems might be
helped if FA balance is restored while he or she still a
child. To achieve this we must be sure that nursing moth-
ers have adequate ALA, and DHA in their diets.
Because the brain is predominantly made of fat,
Acta Neurologica Taiwanica Vol 18 No 4 December 2009
almost all of its structures and functions have a crucial
dependency upon EFAs, which we get directly from our
In the brain, there is little LA or ALA. The brain
prefers arachidonic acid (AA) and DHA. For the brain,
these two fatty acids might be considered essential(17). In
a developing fetus, AA is taken from the mother to help
develop the fetal brain. In infancy, AA is present in
breast milk to further promote brain development. At
about one year, a child is normally able to make enough
of its own AA(18). Thus, for the adult, dietary AA is no
longer as important. Actually, when AA levels are too
high in the lipids of cell membranes, there is a tendency
toward formation of inflammatory substances such as
prostaglandin E2, leukotrienes, and thromboxane A2.
Over the past two decades we have learned that DHA is
the critical long-chain omega-3 fatty acid found in the
brain. Our bodies have the ability to make DHA from
essential fatty acid ALA, but this process is often very
inefficient(19). Thus we seem to have a requirement for
preformed DHA in the diet that cannot be met by other
fatty acids. In this way, DHA may be a conditionally
EFA and essential for the brain.
Beyond their important role in building the brain
structure, EFAs have another crucial role -- as messen-
gers. EFAs are involved in the synthesis and functions of
brain neurotransmitters, and in the molecules of the
immune system(20). It is noted that omega-3 deficiency
reduces the dopamine vesicle density in the cortex and
causes malfunction of the dopaminergic mesocorticolim-
bic pathway(21). The role of EFAs in immune function is
complicated since omega-3 and omega-6 have different
effects on various immune components and is largely
dependent on the omega-3 to omega-6 ratio. Several
mechanisms have been proposed for EFAs to mediate
their immunological functions in several disorders such
as Alzheimer and schizophrenia. These include mem-
brane fluidity (changes that might effect the capability of
cytokines to bind to their respective receptors on the cell
membrane); lipid peroxidation (decrease in free radical-
induced tissue damage); prostaglandin production (an
indirect mechanism whereby prostaglandins, which are
derivatives of PUFA, modify cytokine activity); and reg-
ulation of gene expression (PUFA influences on the
signal transduction pathways and modifies mRNA activ-
FAs that form the structure of your cell membranes
become messengers when a call to action is sent out.
Neuronal membranes contain phospholipid pools that are
the reservoirs for the synthesis of specific lipid messen-
gers on neuronal stimulation or injury(23). These messen-
gers in turn participate in signaling cascades that can
either promote neuronal injury or neuroprotection.
Prostaglandins are synthesized as a result of cyclooxyge-
nase activity. In the f irst step of the AA cascade, the
short-lived precursor, prostaglandin H2, is synthesized.
Additional steps in the cascade result in the synthesis of
an array of prostaglandins, which participate in numer-
ous physiological and neurological processes(24). The
prostaglandins derived from membrane EFAs include
PGE1, PGE2, and PGE3. PGE1 is important in the ner-
vous system as it affects the release of compounds from
nerve cells that transmit nerve impulses. It tends to have
anti-inflammatory properties and is immune enhancing.
PGE2 is a highly inflammatory substance. It can cause
swelling, increased pain sensitivity, and increased blood
viscosity. Leukotrienes are related to PGE2 in that they
are made from the fatty acid AA. PGE3 tends to be mild-
ly anti-inflammatory and immune enhancing. It is
thought to counter the effects of the powerful inflamma-
tory PGE2. It prevents blood platelets from clumping
and helps prevent blood vessel spasm. FAs important in
PGE3 formation, like EPA and DHA, can also reduce
AA in the cells. This reduces the chance of producing
messengers from AA and is one way that these FAs can
alter the production of highly inflammatory messengers.
In another way, the membrane DHA might play a role of
neuroprotection. It is the precursor of oxygenation prod-
ucts now known as the docosanoids, some of which are
powerful counter-proinflammatory mediators. The medi-
ator 10,17S-docosatriene (neuroprotectin D1, NPD1)
counteracts leukocyte infiltration, NF-kappa activation,
and proinflammatory gene expression in brain ischemia-
reperfusion and is an apoptostatic mediator, potently
counteracting oxidative stress-triggered apoptotic DNA
damage in retinal pigment epithelial cells(23).
Acta Neurologica Taiwanica Vol 18 No 4 December 2009
Given the fatty nature of the brain, it seems quite
logical that the mental performance of some individuals
with FA imbalance might be affected. Hibbeln et al.(25)
recently have reported beneficial effects on child devel-
opment with maternal seafood intakes of more than 340
g per week. They found that maternal seafood intake
during pregnancy of less than 340 g per week was asso-
ciated with increased risk of their children being in the
lowest quartile for verbal intelligence quotient. In addi-
tion, low maternal seafood intake was also associated
with increased risk of suboptimum outcomes for proso-
cial behaviour, fine motor, communication, and social
development scores. In another study, Lucas A(26) also
pointed to a beneficial effect of human milk on neurode-
velopment. Children who had consumed mother’s milk
in the early weeks of life had a significantly higher IQ at
7.5-8 years than did those who received no maternal
milk. There was a dose-response relation between the
proportion of mother’s milk in the diet and subsequent
IQ. Furthermore, there is also evidence that healthy indi-
viduals can expect cognitive benefit from EFAs, mainly
EPA and DHA. Fontani et al.(27) conducted a double-blind
RCT on 33 healthy volunteers ages 22-51. For 35 days,
subjects consumed either 4 g fish oil/day ( 800 mg DHA
and 1,600 mg EPA) or 4 g olive oil as placebo. The
DHA/EPA group improved significantly over placebo on
several mood parameters: vigor, anger, anxiety, fatigue,
depression, and confusion. Measures of attention and
reaction time were also improved. Participants demon-
strated marked improvement in sustained attention and a
significant reduction in errors on the attention test.
Accelerated cognitive decline in middle age can
make an individual more vulnerable to dementia in later
life. Evidence is accumulating to suggest omega-3 FA
deficiency contributes to accelerated cognitive decline.
An epidemiology team led by Kalmijn tested 1,613 sub-
jects, ages 45-70, for various cognitive functions at base-
line and after five years and correlated the results with
habitual food consumption reported on a self-adminis-
tered food questionnaire(28). Subjects exhibiting the most
impaired cognitive function (lowest 10 percent of the
group score) also had the lowest intake of DHA/EPA or
fatty fish. Overall cognitive performance and psychomo-
tor speed were positively correlated with DHA/EPA sta-
tus. High intakes of cholesterol and saturated fat were
both linked to increased cognitive impairment in this
middle-aged population.
Recent studies have associated deficits in DHA
abundance with cognitive decline during aging and in
neurodegenerative disease(29). The importance of DHA-
derived NPD1 has been underscored in the homeostatic
regulation of brain cell survival and repair involving neu-
rotrophic, antiapoptotic and antiinflammatory signaling.
Emerging evidence suggests that NPD1 synthesis is acti-
vated by growth factors and neurotrophins. It has impor-
tant determinant and regulatory interactions with the
molecular-genetic mechanisms affecting beta-amyloid
precursor protein and amyloid beta peptide neurobiology.
DHA/EPA in relation to dementia and mild
cognitive impairment
In the past decade, epidemiological studies indicate
relatively high DHA and EPA intake is linked to lower
relative risk of dementia incidence or progression. In
1997, Kalmijn et al.(30) reported on a longitudinal cohort
study, in which 5,386 participants ages 55 or older were
screened for dementia. Dietary habits were evaluated
using a semi-quantitative food frequency questionnaire
and then re-evaluated after 2.1 years. Fish consumption
was inversely related to dementia incidence (RR=0.4,
95% CI=0.2-0.9), and more specifically to the risk of
developing Alzheimer’s disease (RR=0.3, 95% CI=0.1-
0.9). In a Chicago community study, 815 residents ages
65-94 were evaluated via a self-reported food question-
naire and tracked for an average 3.9 years(31). A total of
131 participants developed Alzheimer’s disease. Those
who consumed a fish meal once weekly had a statistical-
ly significant 60-percent decreased risk of Alzheimer’s
disease, compared with those who rarely or never ate
fish (RR=0.4, 95% CI=0.2-0.9). Total omega-3 and
DHA intake, but not EPA intake alone, were significant-
ly associated with this lessened Alzheimer risk. This
suggests an intake of as little as 30 mg/day DHA/EPA
from fish might confer more protection against cognitive
decline than eating no fish at all.
Longitudinal cohort studies can be more objective
when blood or tissue is analyzed for specific nutrients.
As part of the U.S. Framingham Heart Study, a cohort of
899 men and women (median age 76 years), who were
free of dementia at baseline, were followed for a mean
9.1 years for development of all-cause dementia and
Alzheimer’s disease(32). Ninety-nine new cases of demen-
tia (including 71 of Alzheimer’s disease) occurred.
Baseline and follow-up blood samples were tested for
fatty acids in the plasma phospholipid fraction. After
controlling for other variables, subjects in the upper
quartile of plasma phospholipid DHA levels had approx-
imately half the relative risk of developing all-cause
dementia (RR=0.53, 95% CI=0.29-0.97; p0.04) com-
pared to subjects in the three lower quartiles. The upper
quartile (n=488) had a mean DHA intake of 180 mg/day
and a mean fish intake of 3.0 servings per week
(p<0.001). In 2006, a team from Stockholm’s Karolinska
University Hospital published a double-blind RCT of
DHA and EPA for 174 patients with mild-to-moderate
Alzheimer’s disease(33). Patients received either 1.7 g
DHA and 0.6 g EPA daily or a placebo for six months,
after which all received the DHA/EPA supplements for
six more months. After the first six months, decline in
cognitive function did not differ between groups.
However, in a subgroup with less severe cognitive dys-
function (Mini-Mental State Exam score >27 points), a
significantly slower decline was observed in the
DHA/EPA group. A similar slowing was observed in the
placebo group after crossover to DHA/EPA for the sec-
ond six months. These findings suggest patients with
mild Alzheimer deterioration could benefit from taking a
mixed dietary supplement formulation containing both
DHA and EPA.
Mild cognitive impairment (MCI) is currently the
condition most predictive for subsequent progression to
dementia. MCI features severely impaired memory with-
out substantial loss of other cognitive functions.
Approximately 10-15 percent of MCI subjects progress
to dementia within a year of diagnosis. Individuals cog-
nitively impaired but not demented tend to have abnor-
mally low blood levels of DHA and EPA(34).
In a recent systematic review(35), Issa AM et al. found
a trend in favor of omega-3 FAs (fish and total omega-3
consumption) toward reducing risk of dementia and
improving cognitive function. Although the available
data are insufficient to draw strong conclusions about the
effects of omega-3 FAs on cognitive function in normal
aging or on the incidence or treatment of dementia they
still suggest a possible association between omega-3 FAs
and reduced risk of dementia.
EPA and Huntington disease
Huntington disease (HD) features abnormal multipli-
cation of a specific DNA sequence on chromosome 4:
cytosine-adenine-guanine (CAG). Healthy people have
just one CAG sequence at this spot; people with HD can
have several dozen CAG sequences. As a rule, the more
CAGs the HD patient has, the more severe their dis-
ease(36). On a suspicion that certain omega-3 responsive
pathways could be involved, a team of British
researchers have been using purified EPA in its ethyl
ester form (“ethyl-EPA”) as potential therapy for HD(37).
They conducted a small RCT with ethyl-EPA on seven
in-patients with advanced (stage III) HD. After six
months, the four patients who received ethyl-EPA
demonstrated improvement on the orofacial component
of the Unified Huntington Disease Rating Scale, while
the three placebo patients had deteriorated (p<0.03).
MRI brain scans revealed the placebo was associated
with progressive cerebral atrophy and ethyl-EPA was
associated with beneficial changes. Three years later, the
group completed a multicenter, double-blind RCT(38). A
total of 135 Huntington patients received either 2 g/day
ethyl-EPA or placebo. The primary endpoint was the
score at 12 months on the Total Motor Score 4 (TMS-4)
subscale. The ethyl-EPA group as a whole failed to show
statistically significant improvement on TMS-4.
Nevertheless, a subgroup including patients with fewer
CAG showed significantly better TMS-4 improvement(39).
Omega-3 FAs and depression
If omega-3 FAs play a role in depressive disorders,
then it would be expected that countries consuming
greater amounts of these FAs (primarily through fish
intake) would have a lower prevalence of depression.
Acta Neurologica Taiwanica Vol 18 No 4 December 2009
Actually, in a research conducted by Joseph Hibbeln of
the National Institutes of Health it was found that a sig-
nificant negative correlation between worldwide fish
consumption and prevalence of depression(40). In another
research involving a random sample within a nation, fre-
quent fish consumption in the general population is asso-
ciated with a decreased risk of depression(41).
Maternal postpartum depression (also called “perina-
tal depression”) has been linked to omega-3 FA deficien-
cy. As reviewed in Freeman(42), a survey of mother’s milk
in 23 countries determined that lower DHA content or
lower seafood consumption was associated with higher
rates of postpartum depression. Freeman noted that pilot
trials of supplementation with DHA and EPA have pro-
duced mixed results and called for larger and better-
designed trials to resolve this condition that endangers
both mother and child.
Su and colleagues(43) recently reported a beneficial
effect of omega-3 FAs in a 8 week duration double-blind
placebo controlled trial of 22 patients with major depres-
sive disorder using fish oil (daily dose of 2.2 g/day EPA
and 1.1 g/day DHA) or an olive oil placebo. Of the
patients completing the trial, the omega-3 FA group
achieved a significantly greater reduction in depressive
symptoms than the placebo group. In a recent meta-ana-
lytic review of double-blind, placebo-controlled trials of
antidepressant efficacy of omega-3 FAs, Lin PY and his
colleague(44) reviewed ten double-blind, placebo-con-
trolled studies in patients with mood disorders receiving
omega-3 FAs with the treatment period lasting 4 weeks
or longer. They found a significant antidepressant effect
of omega-3 FAs (effect size = 0.61, p= .003) and the
dosage of EPA did not change the antidepressant effica-
cy significantly. However, signif icant heterogeneity
among these studies and publication bias were noted.
They therefore concluded that it is still premature to vali-
date this finding due to publication bias and heterogene-
ity. More large-scale, well-controlled trials are needed to
find out the favorable target subjects, therapeutic dose of
EPA, and the composition of omega-3 FAs in treating
Omega-3 FAs and bipolar disorder
Bipolar disorder (BD) with its complex spectrum of
symptoms is likely associated with neural cell membrane
dysfunction, most likely signal transduction abnormali-
ties. The levels of seafood intake per capita in various
countries of the world roughly correlate with the respec-
tive prevalence rates of BD in community samples(45).
The greater the seafood consumption per capita in a
country, the lower the prevalence of bipolar spectrum
disorders. Countries that consume a lot of fish on aver-
age (e.g., Iceland, Korea, and Taiwan) have relatively low
incidence, while countries that consume very little fish
(e.g., Germany, Switzerland, and Hungary) have up to
seven times the incidence of countries with high fish
intake. Noaghiul and Hibbeln estimated a “vulnerability
threshold” for BD at seafood consumption below 50
pounds of seafood/person/year.
To date, four published double-blind trials on
DHA/EPA for BD have been published. The first was a
1999 trial that found significantly longer remission of
bipolar symptomology from a high-dose DHA and EPA
mixture (9.6 g/day) compared to placebo(46). Three more
double-blind trials were published in 2006 with differing
results. In the largest trial, Frangou et al found signifi-
cant improvement using EPA only (ethyl-EPA) in 75
patients, with 1 g/day working just as well as 2 g/day(47).
Keck et al found no significant differences between
placebo and 6 g/day EPA (no DHA) in 61 patients(48).
Marangell et al conducted a small study on 10 patients
using only DHA and reported only that DHA was “well
tolerated”(49). In a recent Cochrane review Montgomery P
et al.(50) found that only one study, involving 75 partici-
pants, provided data for analysis and showed positive
effects of omega-3 as an adjunctive treatment for depres-
sive but not manic symptoms in bipolar disorder from
five studies. But they concluded that these findings must
be regarded with caution owing to the limited data avail-
Omega-3 FA and schizophrenia
FAs have also been the focus of intense study in the
psychotic disorder schizophrenia(51). A “phospholipid
membrane hypothesis of schizophrenia”, as reviewed in
2000 by Fenton and colleagues(52), encompasses abnor-
malities of long-chain omega-6 FAs such as AA, as well
as DHA and EPA. Fenton et al. list multiple analyses of
Acta Neurologica Taiwanica Vol 18 No 4 December 2009
RBC membranes (recognized markers for EFA status)
that consistently document depletion of AA, DHA, and
EPA. Also noted were studies documenting depletion in
plasma, thrombocytes, and post-mortem brain tissue of
schizophrenia patients(52).
Six double-blind RCTs with DHA/EPA have been
conducted recently, involving 390 patients with schizo-
phrenia or schizoaffective disorder(53-57). Four of these
documented clinical benefit from 2/g EPA daily for three
months. One trial found high-EPA fish oil performed
better than high-DHA fish oil or placebo(53). Another
dose-ranging trial of ethyl-EPA found 2 g/day worked
better than 1 g or 4 g daily(54). Two trials by the same
group examined ethyl-EPA’s effect on tardive dyskinesia
associated with pharmaceutical management of schizo-
phrenia. In a 2002 trial, Emsley et al found benefit at 3
g/day(55), but a later 2006 trial did not demonstrate bene-
fit at the lower dose of 2 g/day(57). Because all these clini-
cal studies using omega 3 FA supplementation showed
the inconsistent results in different doses of ethyl-EPA as
compared with placebo a recent Cochrane review(58) con-
cluded that the use of omega-3 FAs for schizophrenia
still remains experimental and a large well designed,
conducted studies is needed.
EPA supplementation in borderline personality
Borderline personality disorder may also respond to
omega-3 supplementation. In a double blind, placebo-
controlled trial, 30 female subjects with moderately
severe BPD received 1 g/day EPA only (as ethyl-EPA) or
a placebo for two months. Those taking ethyl-EPA expe-
rienced significantly diminished aggression and less
severe depression(59).
As we better understand the brain’s critical depen-
dence on specific EFAs, correct intake of the appropriate
diet or supplements becomes one of the appropriate tasks
we undertake in pursuit of optimal wellness. In this
review, we may have gathered the impression that
omega-3 FAs are more important than omega-6 FAs.
That’s because most modern diets contain too much
omega-6 and far too little omega-3. In reality, balance of
EFAs is critical. We don’t want to go overboard on any
particular FA.
How does one know whether supplementation is
necessary? Physical signs and symptoms of deficiency
include excessive thirst, frequent urination, rough dry
hair and skin, and follicular keratosis(60). The current
knowledge base on DHA/EPA for brain function does
not generate a rational daily intake recommendation.
Hibbeln, from his studies on national seafood intakes
and affective disorder incidence, suggested pregnant
women might want to consume a minimum 650 mg/day
of DHA and EPA (with a minimum 300 mg/day of
DHA) to prevent postpartum depression(40). Although
high doses of ALA can increase tissue EPA levels, ALA
does not have the same effect on DHA levels(61), render-
ing supplementation necessary. For vegetarians cultivat-
ed microalgae are a good source of DHA.
Although the current clinical literature on EFAs for
brain function is still relatively small compared to the lit-
erature on circulatory benefits, the weight of the current
evidence strongly supports their utility for cognition,
behavior, and mood, as well as for early brain develop-
ment and overall mental performance. As we further
unlock the mystery of how FAs affect the brain, we may
be able to change the course of our individual lives and
perhaps even society by making wise dietary changes.
1. Singh M. Essential fatty acids, DHA and human brain.
Indian J Pediatr 2005;72:239-42.
2. Das UN. Essential Fatty acids- a review. Curr Pharm
Biotechnol 2006;7:467-82.
3. Fernstrom JD. Effects of dietary polyunsaturated fatty acids
on neuronal function. Lipids 1999;34:161-9.
4. Simopoulos AP. Evolutionary aspects of diet, the omega-
6/omega-3 ratio and genetic variation: nutritional implica-
tions for chronic diseases. Biomed Pharmacother 2006;60:
Acta Neurologica Taiwanica Vol 18 No 4 December 2009
5. Yehuda S, Rabinovitz S, Mostofsky DI. Essential fatty
acids and the brain: from infancy to aging. Neurobiol
Aging 2005;26:98-102.
6. Salvati S, Attorri L, Avellino C, et al. Diet, lipids and brain
development. Dev Neurosci 2000;22:481-7.
7. Stockard JE, Saste MD, Benford VJ, et al. Effect of docosa-
hexaenoic acid content of maternal diet on auditory brain-
stem conduction times in rat pups. Dev Neurosci 2000;22:
8. Das UN. Essential fatty acids: biochemistry, physiology
and pathology. Biotechnol J 2006;1:420-39.
9. Plourde M, Cunnane SC. Extremely limited synthesis of
long chain polyunsaturates in adults: implications for their
dietary essentiality and use as supplements. Appl Physiol
Nutr Metab 2007;32:619-34.
10. Nightingale S, Woo E, Smith AD, et al. Red blood cell and
adipose tissue fatty acids in mind inactive multiple sclero-
sis. Acta Neurol Scand 1990;82:43-50.
11. Adams PB, Lawson S, Sanigorski A, et al. Arachidonic
acid to eicosapentaenoic acid ratio in blood correlates posi-
tively with clinical symptoms of depression. Lipids 1996;
12. Stevens LJ, Zentall SS, Abate ML, et al. Omega-3 fatty
acids in boys with behavior, learning, and health problems.
Physiol Behav 1996;59:915-20.
13. Clandinin MT, Jumpsen J, Suh M. Relationship between
fatty acid accretion, membrane composition, and biologic
functions. J Pediatr 1994;125:S25-32.
14. Uauy R, Dangour AD. Nutrition in brain development and
aging: role of essential fatty acids. Nutr Rev 2006;64(5 Pt
15. Makrides M, Neumann MA, Byard RW, et al. Fatty acid
composition of brain, retina, and erythrocytes in breast- and
formula-fed infants. Am J Clin Nutr 1994;60:189-94.
16. Innis SM. Dietary (n-3) fatty acids and brain development.
J Nutr 2007;137:855-9.
17. Hadders-Algra M. Prenatal long-chain polyunsaturated
fatty acid status: the importance of a balanced intake of
docosahexaenoic acid and arachidonic acid. J Perinat Med
18. Agostoni C. Role of long-chain polyunsaturated fatty acids
in the first year of life. J Pediatr Gastroenterol Nutr 2008;
19. Brenna JT, Salem N Jr, Sinclair AJ, et al. Alpha-Linolenic
acid supplementation and conversion to n-3 long-chain
polyunsaturated fatty acids in humans. Prostaglandins
Leukot Essent Fatty Acids 2009;80:85-91.
20. Yehuda S, Rabinovitz S, Mostofsky DI. Essential fatty
acids and the brain: from infancy to aging. Neurobiol
Aging 2005;26:98-102.
21. Yehuda S, Rabinovitz S, Carasso RL, et al. Fatty acids and
brain peptides. Peptides 1998;9:407-19.
22. Yao JK, van Kammen DP. Membrane phospholipids and
cytokine interaction in schizophrenia. Int Rev Neurobiol
23. Bazan NG. Lipid signaling in neural plasticity, brain repair,
and neuroprotection. Mol Neurobiol 2005;32:89-103.
24. Privett OS, Phillips F, Fukazawa T, et al. Studies on the
relationship of the synthesis of prostaglandins to the biolog-
ical activity of essential fatty acid. Biochim Biophys Acta
25. Hibbeln JR, Davis JM, Steer C, et al. Maternal seafood
consumption in pregnancy and neurodevelopmental out-
comes in childhood (ALSPAC study): an observational
cohort study. Lancet 2007;369:578-85.
26. Lucas A, Morley R, Cole TJ, et al. Breast milk and subse-
quent intelligence quotient in children born preterm. Lancet
27. Fontani G, Corradeschi F, Felici A, et al. Cognitive and
physiological effects of Omega-3 polyunsaturated fatty acid
supplementation in healthy subjects. Eur J Clin Invest
28. Kalmijn S, van Boxtel MP, Ocke M, et al. Dietary intake of
fatty acids and fish in relation to cognitive performance at
middle age. Neurology 2004;62:275-80.
29. Lukiw WJ, Bazan NG. Docosahexaenoic acid and the aging
brain. J Nutr 2008;138:2510-4.
30. Kalmijn S, Launer LJ, Ott A, et al. Dietary fat intake and
the risk of incident dementia in the Rotterdam Study. Ann
Neurol 1997;42:776-82.
31. Morris MC, Evans DA, Bienias JL, et al. Consumption of
fish and n-3 fatty acids and risk of incident Alzheimer dis-
ease. Arch Neurol 2003;60:940-6.
32. Schaefer EJ, Bongard V, Beiser AS, et al. Plasma phos-
phatidylcholine docosahexaenoic acid content and risk of
dementia and Alzheimer disease: the Framingham Heart
Study. Arch Neurol 2006;63:1545-50.
33. Freund-Levi Y, Eriksdotter-Jonhagen M, Cederholm T, et
Acta Neurologica Taiwanica Vol 18 No 4 December 2009
al. Omega-3 fatty acid treatment in 174 patients with mild
to moderate Alzheimer disease: OmegAD study: a random-
ized double-blind trial. Arch Neurol 2006;63:1402-8.
34. Conquer JA, Tierney MC, Zecevic J, et al. Fatty acid analy-
sis of blood plasma of patients with Alzheimer’s disease,
other types of dementia, and cognitive impairment. Lipids
35. Issa AM, Mojica WA, Morton SC, et al. The efficacy of
omega-3 fatty acids on cognitive function in aging and
dementia: a systematic review. Dement Geriatr Cogn
Disord 2006;21:88-96.
36. Martin JB, Gusella JF. Huntington’s disease. Pathogenesis
and management. N Engl J Med 1986;315:1267-76.
37. Puri BK, Bydder GM, Counsell SJ, et al. MRI and neu-
ropsychological improvement in Huntington disease fol-
lowing ethyl-EPA treatment. Neuroreport 2002;13:123-6.
38. Puri BK, Leavitt BR, Hayden MR, et al. Ethyl-EPA in
Huntington disease: a double-blind, randomized, placebo-
controlled trial. Neurology 2005;65:286-92.
39. Murck H, Manku M. Ethyl-EPA in Huntington disease:
potentially relevant mechanism of action. Brain Res Bull
40. Hibbeln JR. Fish consumption and major depression.
Lancet 1998;351:1213.
41. Tanskanen A, Hibbeln JR, Hintikka J, et al. Fish consump-
tion, depression, and suicidality in a general population.
Arch Gen Psychiatry 2001;58:512-3.
42. Freeman MP. Omega-3 fatty acids and perinatal depression:
a review of the literature and recommendations for future
research. Prostaglandins Leukot Essent Fatty Acids
43. Su KP, Huang SY, Chiu CC, et al. Omega-3 fatty acids in
major depressive disorder.A preliminary double-blind,
placebo-controlled trial. Eur Neuropsychopharmacol
44. Lin PY, Su KP. A meta-analytic review of double-blind,
placebo-controlled trials of antidepressant efficacy of
omega-3 fatty acids. J Clin Psychiatry. 2007;68:1056-61.
45. Noaghiul S, Hibbeln JR. Cross-national comparisons of
seafood consumption and rates of bipolar disorders. Am J
Psychiatry 2003;160:2222-7.
46. Stoll AL, Severus WE, Freeman MP, et al. Omega 3 fatty
acids in bipolar disorder: a preliminary double-blind, place-
bo-controlled trial. Arch Gen Psychiatry 1999;56:407-12.
47. Frangou S, Lewis M, McCrone P. Efficacy of ethyl-eicos-
apentaenoic acid in bipolar depression: randomised double-
blind placebo-controlled study. Br J Psychiatry 2006;188:
48. Keck PE Jr, Mintz J, McElroy SL. Double-blind, random-
ized, placebo-controlled trials of ethyl-eicosapentanoate in
the treatment of bipolar depression and rapid cycling bipo-
lar disorder. Biol Psychiatry 2006;60:1020-2.
49. Marangell LB, Suppes T, Ketter TA. Omega-3 fatty acids in
bipolar disorder: clinical and research considerations.
Prostaglandins Leukot Essent Fatty Acids 2006;75:315-21.
50. Montgomery P, Richardson AJ. Omega-3 fatty acids for
bipolar disorder. Cochrane Database Syst Rev 2008;(2):
51. American Psychiatric Association: Diagnostic and statisti-
cal manual of mental disorders. Fourth edit. Washington,
DC: American Psychiatric Association, 1994.
52. Fenton WS, Hibbeln J, Knable M. Essential fatty acids,
lipid membrane abnormalities, and the diagnosis and treat-
ment of schizophrenia. Biol Psychiatry 2000;47:8-21.
53. Peet M, Brind J, Ramchand CN, et al. Two double-blind
placebo-controlled pilot studies of eicosapentaenoic acid in
the treatment of schizophrenia. Schizophr Res 2001;49:
54. Peet M, Horrobin DF, E-E Multicentre Study Group. A
dose-ranging exploratory study of the effects of ethyl-eicos-
apentaenoate in patients with persistent schizophrenic
symptoms. J Psychiatr Res 2002;36:7-18.
55. Emsley R, Myburgh C, Oosthuizen P, et al. Randomized,
placebo-controlled study of ethyl-eicosapentaenoic acid as
supplemental treatment in schizophrenia. Am J Psychiatry
56. Fenton WS, Dickerson F, Boronow J, et al. A placebo-con-
trolled trial of omega-3 fatty acid (ethyl eicosapentaenoic
acid) supplementation for residual symptoms and cognitive
impairment in schizophrenia. Am J Psychiatry 2001;158:
57. Emsley R, Niehaus DJ, Koen L, et al. The effects of eicos-
apentaenoic acid in tardive dyskinesia: a randomized,
placebo-controlled trial. Schizophr Res 2006;84:112-20.
58. Joy CB, Mumby-Croft R, Joy LA. Polyunsaturated fatty
acid supplementation for schizophrenia. Cochrane Database
Syst Rev 2006;3:CD001257.
59. Zanarini MC, Frankenburg FR. Omega-3 fatty acid treat-
Acta Neurologica Taiwanica Vol 18 No 4 December 2009
ment of women with borderline personality disorder: a dou-
ble-blind, placebo-controlled pilot study. Am J Psychiatry
60. Richardson AJ. Omega-3 fatty acids in ADHD and related
neurodevelopmental disorders. Int Rev Psychiatry 2006;
61. Francois CA, Connor SL, Bolewicz LC, et al. Supple-
menting lactating women with flaxseed oil does not
increase docosahexaenoic acid in their milk. Am J Clin
Nutr 2003;77:226-33.
Acta Neurologica Taiwanica Vol 18 No 4 December 2009
... Importantly, ALA can be converted to long-chain PUFAs (LCPUFA) in the liver, allowing the synthesis of EPA and DHA acids. DHA is the predominant fatty acid in the brain, constituting about 15% of the total fatty acid in that tissue [47]. As well, low intake of DHA led to poor performance in attentions and learning tests [48], along with elevated aggression and anxiety levels [49] in rodents. ...
Full-text available
Brain physiology and morphology are vulnerable to chronic stress, affecting cognitive performance and behavior. However, functional compounds found in food may alleviate these alterations. White quinoa (Chenopodium quinoa, Wild) seeds have high content of n-3 fatty acids, including alpha-linolenic acid. This work aimed to evaluate the possible neuroprotective role of a quinoa-based functional food (QFF) in rats. Prepubertal male Sprague-Dawley rats were fed with rat chow or QFF (50% rat chow + 50% dehydrated quinoa seeds) and exposed or not to restraint stress protocol (2 hours/day; 15 days). Four experimental groups were used: Non-stressed (rat chow), Non-stressed + QFF, Stressed (rat chow) and Stressed + QFF. Weight gain, locomotor activity (open field), anxiety (elevated plus maze, light-dark box), spatial memory (Y-maze), and dendritic length in the hippocampus were measured in all animals. QFF intake did not affect anxiety-like behaviors, while the memory of stressed rats fed with QFF improved compared to those fed with rat chow. In addition, QFF intake countered the stress-induced dendritic atrophy in pyramidal neurons located in CA3 area of the hippocampus. The results suggest that a quinoa-supplemented diet could have a protective role on the memory of chronically stressed rats.
... The findings of this study revealed that lung and liver tissue were effectively dissolved using a 10% KOH solution after 76 h at 37 • C, while brain tissue was not. The inefficient dissolution of brain tissue is likely attributed to its high lipid content, which may necessitate the use or addition of organic solvents like methanol/chloroform and should be explored in future investigations [36,37]. ...
Full-text available
Microplastic particles are ubiquitous in our environment, having entered the air, the water, the soil, and ultimately our food chain. Owing to their small size, these particles can potentially enter the bloodstream and accumulate in the organs. To detect microplastics using existing methods, they must first be isolated. The aim of this study was to develop a non-destructive method for efficiently and affordably isolating plastic particles. We investigated the digestion of kidney, lung, liver, and brain samples from pigs. Kidney samples were analyzed using light microscopy after incubation with proteinase K, pepsin/pancreatin, and 10% potassium hydroxide (KOH) solution. Various KOH:tissue ratios were employed for the digestion of lung, liver, and brain samples. Additionally, we examined the effect of 10% KOH solution on added polystyrene microplastics using scanning electron microscopy. Our findings revealed that a 10% KOH solution is the most suitable for dissolving diverse organ samples, while enzymatic methods require further refinement. Moreover, we demonstrated that commonly used 1 µm polystyrene particles remain unaffected by 10% KOH solution even after 76 h of incubation. Digestion by KOH offers a simple and cost-effective approach for processing organ samples and holds potential for isolating plastic particles from meat products.
... However, the relevance of these studies requires further longitudinal cohort studies or randomized controlled trials to validate the role of LA in ADHD and ASD. Therefore, this is an area of future research and the different patterns of fatty acid combinations, the duration of interventions, and the dosage used to treat ADHD and ASD need to be further investigated [122]. ...
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Purpose Attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are prevalent neurodevelopmental disorders caused by genetic and environmental factors. The basic brain processes or biomarkers of novel ADHD/ASD medication targets are yet unknown. Observational studies have linked polyunsaturated fatty acids (PUFAs) to ADHD/ASD, but the causative linkages are unknown. Methods A large genome-wide association study (GWAS) was pooled to give summary statistics on unsaturated fatty acids and ADHD/ASD utilizing a multivariate Mendelian randomization (MVMR) research design. DHA, LA, omega-3, and omega-6 fatty acids were examined in ADHD/ASD GWAS data. Inverse variance weighting (IVW) and MR-Egger and outlier point tests (MR-PRESSO) were used to evaluate data from univariate Mendelian randomization analysis of significant genetic connections with PUFA levels (P < 5 × 10⁻⁸). The odds ratio (OR) and 95% CI for MVMR analysis utilizing IVW were calculated using combinations of single nucleotide polymorphisms (SNPs) as a composite proxy for fatty acids. Results There was some degree of causality between genetically predicted LA and both susceptibilities (ADHD, OR = 0.898, 95% CI = 0.806–0.999, P = 0.049; ASD: OR = 2.399, 95% CI = 1.228–4.688, P = 0.010). However, other PUFAs were not associated with ADHD/ASD. Conclusion LA appears to be a substantial, independent cause of ADHD and ASD. LA may treat ADHD but worsen ASD. LA's function in ADHD and ASD needs additional longitudinal cohorts or randomized controlled studies.
... While the exact mechanism is unclear, it has been proposed that certain components of human breastmilk, including human milk oligosaccharides, arachidonic acid, and docosahexaenoic acid, modulate the neurodevelopmental processes of the newborn brain in the first few months after birth, a time of rapid growth and maturation of the brain [6][7][8][9] . From this perspective, if breastfeeding truly has a biological (direct nutritional) effect on intelligence and educational outcomes, we should observe it across all populations and settings, not just in high-income countries. ...
Conference Paper
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Background The benefits of exclusive breastfeeding (EBF) for infant health and survival are well documented. However, its impact on educational outcomes has been contested and poorly researched in Africa. It has been hypothesised that positive associations reported in high-income countries can be attributed to residual confounding by socioeconomic status (SES) because EBF strongly correlates with SES in these settings. Our study investigated whether EBF duration in infancy is associated with educational attainment and age-for-grade trajectories at school-age in rural Malawi. Methods Longitudinal data on 1021 children born to women in the Karonga Demographic Surveillance site in Malawi were analysed. Breastfeeding data was collected in the first three months after birth and again at age one. The school grade of each child was recorded each year from age six, when they started school, until age 13. We calculated age-for-grade based on whether a child was on, over, or under the expected age for a grade. Generalised estimating equations estimated the average effect of EBF on age-for-grade. Latent class growth modelling identified age-for-grade trajectories, and multinomial logistic regression examined their associations with EBF. Maternal-child characteristics and SES were controlled. Stata 17 was used for statistical analysis. Results Only 20.2% of the mothers had at least a secondary education, and slightly more than half (51.9%) of the children were male. Overall, 35.9% of the children were exclusively breastfed for six months. Over-age for grade steadily increased from 9.6% at age eight to 41.9% at thirteen. There was some evidence that EBF for six months was associated with lower odds of over-age for grade than EBF for less than three months (aOR=0.82, 95%CI=0.64–1.06). In subgroup analyses, children exclusively breastfed for six months in infancy were less likely to be over-age for grades between ages six to nine (aOR=0.64, 95%CI=0.43–0.94). Latent class growth analysis identified four distinct age-for-grade trajectories: (1) falling behind from early grades, (2) falling behind from middle grades, (3) falling behind from terminal grades, and (4) consistently on time for grades. There was some evidence that EBF reduced the odds of falling behind in the early school grades (aOR=0.66, 95%CI=0.41–1.08) but not later. Conclusion Our study adds to the growing evidence that EBF for six months has nutritional benefits beyond infant health and survival, supporting the WHO’s recommendation on EBF. It also casts doubt on the hypothesis that beneficial effects reported in high-income settings are due to confounding by socioeconomic status.
... Ułatwiają wchłanianie wapnia, dlatego są niezastąpione w profilaktyce i leczeniu osteoporozy [5,8]. Wzmacniają integralność mózgu i zmniejszają ryzyko rozwoju chorób neurodegeneracyjnych i psychiatrycznych zaburzeń [2]. NNKT nie są wytwarzane w organizmie człowieka i muszą być dostarczane w pokarmie. ...
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Phospholipidomics is a specialized branch of lipidomics that focuses on the characterization and quantification of phospholipids. By using sensitive analytical techniques, phospholipidomics enables researchers to better understand the metabolism and activities of phospholipids in brain disorders such as Alzheimer’s and Parkinson’s diseases. In the brain, identifying specific phospholipid biomarkers can offer valuable insights into the underlying molecular features and biochemistry of these diseases through a variety of sensitive analytical techniques. Phospholipidomics has emerged as a promising tool in clinical studies, with immense potential to advance our knowledge of neurological diseases and enhance diagnosis and treatment options for patients. In the present review paper, we discussed numerous applications of phospholipidomics tools in clinical studies, with a particular focus on the neurological field. By exploring phospholipids’ functions in neurological diseases and the potential of phospholipidomics in clinical research, we provided valuable insights that could aid researchers and clinicians in harnessing the full prospective of this innovative practice and improve patient outcomes by providing more potent treatments for neurological diseases. Graphical Abstract
Traumatic brain injury (TBI), a major cause of morbidity and mortality worldwide, is hard to diagnose at the point of care with patients often exhibiting no clinical symptoms. There is an urgent need for rapid point-of-care diagnostics to enable timely intervention. We have developed a technology for rapid acquisition of molecular fingerprints of TBI biochemistry to safely measure proxies for cerebral injury through the eye, providing a path toward noninvasive point-of-care neurodiagnostics using simultaneous Raman spectroscopy and fundus imaging of the neuroretina. Detection of endogenous neuromarkers in porcine eyes’ posterior revealed enhancement of high–wave number bands, clearly distinguishing TBI and healthy cohorts, classified via artificial neural network algorithm for automated data interpretation. Clinically, translating into reduced specialist support, this markedly improves the speed of diagnosis. Designed as a hand-held cost-effective technology, it can allow clinicians to rapidly assess TBI at the point of care and identify long-term changes in brain biochemistry in acute or chronic neurodiseases.
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The dietary essential PUFA docosahexaenoic acid [DHA; 22:6(n-3)] is a critical contributor to cell structure and function in the nervous system, and deficits in DHA abundance are associated with cognitive decline during aging and in neurodegenerative disease. Recent studies underscore the importance of DHA-derived neuroprotectin D1 (NPD1) in the homeostatic regulation of brain cell survival and repair involving neurotrophic, antiapoptotic and antiinflammatory signaling. Emerging evidence suggests that NPD1 synthesis is activated by growth factors and neurotrophins. Evolving research indicates that NPD1 has important determinant and regulatory interactions with the molecular-genetic mechanisms affecting beta-amyloid precursor protein (betaAPP) and amyloid beta (Abeta) peptide neurobiology. Deficits in DHA or its peroxidation appear to contribute to inflammatory signaling, apoptosis, and neuronal dysfunction in Alzheimer disease (AD), a common and progressive age-related neurological disorder unique to structures and processes of the human brain. This article briefly reviews our current understanding of the interactions of DHA and NPD1 on betaAPP processing and Abeta peptide signaling and how this contributes to oxidative and pathogenic processes characteristic of aging and AD pathology.
Optimal neurodevelopment of the fetus depends in part on an adequate supply of docosahexaenoic acid (DHA), an omega-3 essential fatty acid that is abundant in seafood. A diet lacking in seafood could impair development because of too little long-chain omega-3 fatty acids such as DHA and eicosapentaenoic acid. Nevertheless, federal agencies have recommended limiting seafood consumption by parturients to 340 g per week so as to avoid exposing the fetus to trace amounts of neurotoxins. The investigators used data from the Avon Longitudinal Study of Parents and Children to clarify the influence of maternal seafood intake during pregnancy on developmental, behavioral, and cognitive outcomes at ages 6 months to 8 years. Participating were 11,875 pregnant women who completed a food frequency questionnaire at 32 weeks’ gestation. Children were assessed using items from the Denver Developmental Screening Test as well as the Strengths and Difficulties Questionnaire and verbal and performance intelligence quotient (IQ) scores. About one-third of women in the study ate up to 340 g of seafood each week, whereas 12% ate no seafood at all while pregnant. Just under one-fourth of women ate more than 340 g weekly. Low seafood consumption correlated with a socially disadvantageous setting including low educational levels and also with less than ideal lifestyles. After adjusting for these and other variables, eating less than 340 g of seafood each week correlated with an increased likelihood of a verbal IQ in the lowest quartile. The odds ratio (OR) for women eating no seafood, compared with those eating more than 340 g weekly, was 1.48 with a 95% confidence interval (CI) of 1.16–1.90. For women eating some seafood but less than 340 per week the OR for low verbal intelligence was 1.09 (95% CI, 0.92–1.29). Low seafood intake also was associated with suboptimal outcomes for prosocial behavior, fine motor function, communicative ability, and social development scores. In each instance, the risk of a suboptimal outcome increased with declining levels of seafood intake. Fewer than 2% of women in this study consumed fish oil supplements while pregnant. Outcomes of infants whose mothers took a supplement but did not eat seafood were similar to those in infants whose mothers did eat seafood. No trend toward benefit in any neurodevelopmental domain was observed when the weekly seafood intake was less than 340 g. These findings suggest that limiting weekly seafood consumption to less than 340 g may have adverse effects on early childhood neurodevelopment. The authors believe that a lack of essential nutrients is more harmful than potential exposure to the trace contaminants present in some seafood.
1.1. Hypophysectomized immature rats developed scaly tails and feet similar to severe dermal symptoms of an essential fatty acid deficiency in less than 8 weeks after the operation in spite of an abundance of linoleate and arachidonate in the diet. There was no effect of hypophysectomy on the interconversion of linoleate to arachidonate.2.2. Studies on the biosynthesis of prostaglandins by the vesicular glands of normal and hypophysectomized sheep indicated that the synthesis of these compounds was impaired by hypophysectomy. These observations suggest that the biological activity of essential fatty acids may be related to prostaglandin synthesis through an endocrine function.
The 2 most abundant long-chain polyunsaturated fatty acids (LCPUFAs) in the brain are docosahexaenoic acid (DHA) and arachidonic acid (ARA), where they have a functional and structural role in infant development. DHA is concentrated in the prefrontal cortex, which is important for association and short-term memory, and in some retinal cells. Concentrations of PUFAs in human breast milk are relatively consistent during the first year of life, and studies have shown that breast-fed infants have a greater mean weight percentage of DHA and a greater proportion of DHA in their red blood cells and brain cortex than formula-fed infants. Furthermore, cortex DHA in breast-fed infants increases with age, probably due to the length of feeding. Maternal supplementation with cod liver oil, which is rich in DHA and eicosapentaenoic acid, improved children's intelligence quotient compared with corn-oil supplementation by 4 years of age. The LCPUFA content of human breast milk is affected by a number of factors, including diet, gestational age, parity, and smoking. Supplementation of formula feed with DHA and ARA results in infant development that is similar to breast-feeding, and may have benefits on blood pressure in later childhood. The beneficial effects of LCPUFA supplementation on visual acuity continue after weaning irrespective of the type of diet. The long-term effects and duration of supplementation of breast- and formula-fed infants requires further investigation.
Blood levels of polyunsaturated fatty acids (PUFA) are considered biomarkers of status. Alpha-linolenic acid, ALA, the plant omega-3, is the dietary precursor for the long-chain omega-3 PUFA eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). Studies in normal healthy adults consuming western diets, which are rich in linoleic acid (LA), show that supplemental ALA raises EPA and DPA status in the blood and in breast milk. However, ALA or EPA dietary supplements have little effect on blood or breast milk DHA levels, whereas consumption of preformed DHA is effective in raising blood DHA levels. Addition of ALA to the diets of formula-fed infants does raise DHA, but no level of ALA tested raises DHA to levels achievable with preformed DHA at intakes similar to typical human milk DHA supply. The DHA status of infants and adults consuming preformed DHA in their diets is, on average, greater than that of people who do not consume DHA. With no other changes in diet, improvement of blood DHA status can be achieved with dietary supplements of preformed DHA, but not with supplementation of ALA, EPA, or other precursors.
There is considerable controversy over whether nutrition in early life has a long-term influence on neurodevelopment. We have shown previously that, in preterm infants, mother's choice to provide breast milk was associated with higher developmental scores at 18 months. We now report data on intelligence quotient (IQ) in the same children seen at 7 1/2-8 years. IQ was assessed in 300 children with an abbreviated version of the Weschler Intelligence Scale for Children (revised Anglicised). Children who had consumed mother's milk in the early weeks of life had a significantly higher IQ at 7 1/2-8 years than did those who received no maternal milk. An 8.3 point advantage (over half a standard deviation) in IQ remained even after adjustment for differences between groups in mother's education and social class (p less than 0.0001). This advantage was associated with being fed mother's milk by tube rather than with the process of breastfeeding. There was a dose-response relation between the proportion of mother's milk in the diet and subsequent IQ. Children whose mothers chose to provide milk but failed to do so had the same IQ as those whose mothers elected not to provide breast milk. Although these results could be explained by differences between groups in parenting skills or genetic potential (even after adjustment for social and educational factors), our data point to a beneficial effect of human milk on neurodevelopment.
The fatty acid profiles of phosphatidyl ethanolamine (PE) and phosphatidyl choline (PC) of the red blood cells of 30 patients with mild inactive multiple sclerosis (MS) and 30 healthy controls were studied by gas chromatography. The groups were well matched for factors likely to influence tissue lipid levels, including diet. The MS patients showed a significant reduction in PE eicosapentaenoic acid (p = 0.009) especially in women, and an increase in both PE dihomo-gamma-linolenic acid (p = 0.004) and PC stearic acid (p = 0.04). No reduction in linoleic acid was observed in either the PC or PE fractions of the MS subjects. A similar study of the fatty acid profile in adipose tissue in 26 MS and 35 healthy controls found no detectable eicosapentaenoic acid in either group. However, whereas docosahexaenoic acid was not detectable in any MS patient, 40% of the controls had measurable levels varying from to 0.1 to 0.3% of total estimated fatty acid (p = 0.0003). No reduction in linoleic acid in MS subjects was observed. Supplementation with oral fish body oil demonstrated that n-3 fatty acids were incorporated into red blood cells over 5 weeks and this occurred equally in MS and controls. The effects of oral supplementation on adipose tissue were studied after 1 and 2 years. Whereas many fatty acids such as linoleic acid were raised at 1 year, but did not rise subsequently, eicosapentaenoic acid and docosahexaenoic acid continued to rise through the 2-year period.(ABSTRACT TRUNCATED AT 250 WORDS)
Huntington's disease is an autosomal dominant disorder that usually begins in mid-life and is characterized by a progression of involuntary choreiform movements, psychological change, and dementia. George Huntington and his father and grandfather first studied the illness in families in East Hampton, Long Island, New York. The ancestry of some cases has been traced to immigrants from Bures, England, in 1649. Other evidence also suggests that the disease is of European origin; cases in South Africa have been traced to Dutch settlers who emigrated there in 1658, and cases in Tasmania have been traced to ancestors from Somerset, England. These data and other evidence suggest that the genetic defect that causes Huntington's disease originated from a common source and that new mutations are rare and possibly nonexistent. A survey is presented.