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brain injury may shift to even higher values for populations at with these variations will have an even lower ability to con-
risk for brain injury. 40,41 vert plant-based omega-3 (e.g., from chia seeds, flax seeds,
and walnuts) into EPA and DHA than a person without these
Impact of O3FA Supplements variations. 44,45 Direct consumption of EPA and DHA (pri-
and Fish Consumption marily from fish) removes the conversion steps as metabolic
Supplementation of O3FAs was associated with higher O3I bottlenecks. This means that EPA and DHA absorbed from
values, even though most of the participants who took supple- supplements or food can directly circulate as anti-inflamma-
ments still had O3I values that fell in the moderate- and high- tory signaling molecules. 46
risk categories. The cross-sectional design of this study and
considerable incomplete or ambiguous survey data regarding This study did not find significant differences in the results
the dose of the supplement prevented a more detailed analysis of the vegan/vegetarian participants owing to the low number
of the relationship between dosage and O3I. However, par- of participants in these categories. In addition to the lack of
ticipants who reported taking O3FA supplements were more consumption of EPA and DHA from fish, plant-based diets
likely to have lower O3I risk status. are more likely to be deficient in choline, a structural compo-
nent of lysophosphatidylcholine and a transporter that allows
Genetics play a role in how people process supplemental omega-3s to cross the blood-brain barrier. 48,49 These factors
O3FA. Genetic variability may explain why some participants would place individuals following a vegan/vegetarian diet at
were still in the high-risk category despite consuming supple- greater risk of having low O3I values, putting them in higher
ments. The apolipoprotein E gene (APOE) has several forms. risk categories. Further research to evaluate the O3FA status
APOE ε4, one of the forms, increases the risk of Alzheimer’s in military personnel who follow vegan/vegetarian diets is
disease. It has been hypothesized that individuals with the warranted.
APOE ε4 form will likely not benefit from fish oil supplemen-
tation where DHA is in a free (commonly found) form because This study’s results showed that more people in the low-risk
they have an impaired brain barrier transport system and the category supplemented with O3FA than consumed fish. Al-
DHA will not cross the blood-brain barrier. This means peo- though additional research should explore this behavior in
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ple who have the APOE ε4 form will not be able to carry the this population, we postulate several potential reasons for this.
O3FA into the brain where it can exert its anti-inflammatory Fish tends to be expensive, particularly in non-coastal states
effects after injury. This is critical to a soldier who is at risk without abundant access to fresh fish, and it has an acquired
for brain injury. One way people with APOE ε4 can obtain taste that not everyone enjoys. Different fish also have differ-
bioavailable EPA and DHA is by consuming fish. If they do ent levels of O3FA, with salmon containing the highest levels;
consume supplements, the supplements must contain a spe- however, it is more expensive. Even more affordable fish, like
cial form of DHA called DHA-lysophosphatidylcholine. More tuna, can vary in O3FA amounts, with some containing very
research evaluating the type of omega-3 supplementation little.
military personnel should use is needed, and the inclusion of
APOE ε4 screening is recommended for a more precise assess- Brain Injury Risk Factors
ment of supplementation requirements. Brain injuries may increase the need for O3FAs, as the body
uses them to build neurons and inflammatory mediators in
Fish consumption was positively associated with O3FA sta- response to the injury. 40,41 Brain injuries are also likely to de-
tus (O3I and O6:O3 ratio), based on both continuous and crease O3FA status, as they are used in the repair process. Ad-
categorical data analysis results. Consistent with the present ditionally, a syndrome known as ‘leaky gut’ that accompanies
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findings, Hanson et al. recently reported a similar relation- brain injuries may also decrease the absorption of O3FA.
ship between fish consumption and O3FA status in a cohort of Leaky gut syndrome results from damage to the lining of the
U.S. Soldiers. While fish consumption was linearly correlated intestinal tract that can be caused by many factors, including a
with O3I, only one of five participants in the low-risk category disruption in the gut-brain axis due to brain injury. 51–53 When
reported fish consumption, although that person also took multiple brain injuries occur in cases with insufficient O3FAs,
O3FA supplements. None of the participants who ate fish but a positive feedback loop may be triggered, where brain injuries
did not take supplements was categorized as low risk based on decrease omega-3 status and decreased omega-3 status impairs
the O3I values. Based on the results from this population, fish resiliency in response to brain injury (Figure 3).
consumption is associated with O3I values, increasing the like-
lihood of having values that are in the moderate-risk category In this study, cluster analysis demonstrated that even though
as opposed to the high-risk category. However, fish consump- the highly exposed cluster (cluster 1) had the highest consump-
tion alone is not sufficient to support low-risk O3I values or tion of O3FA supplements and a high consumption of fish,
an optimal O6:O3 ratio. they had a lower O3I and higher O6:O3 ratio than the mod-
erately exposed (cluster 2) and low exposure (cluster 3) clus-
The associations observed between the impact of fish con- ters. Although this study was not designed to examine cause
sumption and O3FA supplementation on omega-3 status and effect, these associations suggest a higher utilization, and
in this population support the current understanding of therefore higher need, of O3FA in the participants who are
omega-3 status and metabolism. Direct sources of EPA and highly exposed to brain injury risk factors. It is also possible
DHA appear to be the best option for increasing omega-3 that soldiers who had a history of TBI or who were highly
status, as a high O6:O3 ratio limits the internal conversion exposed to brain injury risk factors, consumed omega-3 sup-
of ALA to EPA and DHA to <4%. The pathways that con- plements preventatively. Therefore, research designed to allow
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vert omega-3 into EPA and DHA depend on the FADS1 and for a more detailed analysis of O3FA supplementation dosage
FADS2 genes. Genetic variations in FADS1 and FADS2 may and timing of supplementation compared with the timing of
further impair this pathway (Figure 2). Therefore, a person exposure to brain injury risk factors is warranted.

48 | JSOM Volume 24, Edition 2 / Summer 2024