Download Omega-3 Polyunsaturated Fatty Acids in Physical Performance

International Journal of Sport Nutrition and Exercise Metabolism, 2013, 23, 83 -96
© 2013 Human Kinetics, Inc.
www.IJSNEM-Journal.com
SCHOLARLY REVIEW
Omega-3 Polyunsaturated Fatty Acids in Physical
Performance Optimization
Timothy D. Mickleborough
Increased muscle oxidative stress and inflammatory responses among athletes have been reported consistently.
In addition, it is well known that exhaustive or unaccustomed exercise can lead to muscle fatigue, delayed-onset
muscle soreness, and a decrement in performance. Omega-3 polyunsaturated fatty acids (PUFAs) have been
shown to decrease the production of inflammatory eicosanoids, cytokines, and reactive oxygen species; have
immunomodulatory effects; and attenuate inflammatory diseases. While a number of studies have assessed the
efficacy of omega-3 PUFA supplementation on red blood cell deformability, muscle damage, inflammation,
and metabolism during exercise, only a few have evaluated the impact of omega-3 PUFA supplementation on
exercise performance. It has been suggested that the ingestion of EPA and DHA of approximately 1–2 g/d, at
a ratio of EPA to DHA of 2:1, may be beneficial in counteracting exercise-induced inflammation and for the
overall athlete health. However, the human data are inconclusive as to whether omega-3 PUFA supplementation
at this dosage is effective in attenuating the inflammatory and immunomodulatory response to exercise and
improving exercise performance. Thus, attempts should be made to establish an optimal omega-3 fatty-acid
dosage to maximize the risk-to-reward ratio of supplementation. It should be noted that high omega-3 PUFA
consumption may lead to immunosuppression and prolong bleeding time. Future studies investigating the
efficacy of omega-3 PUFA supplementation in exercise-trained individuals should consider using an exercise
protocol of sufficient duration and intensity to produce a more robust oxidative and inflammatory response.
Keywords: fish oil, exercise, inflammation, PUFAs
Over the past 3 decades, there has been substantial
interest in the therapeutic potential of fish oils for various
inflammatory conditions such as rheumatoid arthritis,
inflammatory bowel diseases, and asthma in humans. In
addition, fish oil, rich in omega-3 polyunsaturated fatty
acids (PUFAs), exerts anti-inflammatory and immunomodulatory effects and may be useful as a nutritional
countermeasure to exercise-induced inflammation and
immune dysfunction in athletes. The omega-3 PUFAs
such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found in fish oil appear to have additional anti-inflammatory properties, primarily through
their effects on the neutrophil and macrophage components of the inflammatory response (Lee et al., 1985).
Initial interest in the cardiovascular benefits of EPA
and DHA was provoked by the finding that the Greenland Eskimos and other populations who consume diets
rich in these fatty acids have remarkably low incidences
of cardiovascular diseases (Dyerberg, Bang, & Hjorne,
1975; Yamori, Nara, Iritani, Workman, & Inagami, 1985).
A large number of both experimental and epidemiological
studies have since been conducted to examine the effect
The author is with the Dept. of Kinesiology, Indiana University,
Bloomington, IN.
of consuming fish oil, which contains high amounts of
EPA and DHA, on cardiovascular health, with most showing an inverse correlation on morbidity and mortality
(Albert et al., 2002; Hu et al., 2002; Lemaitre et al., 2003;
Oomen et al., 2000; Rissanen, Voutilainen, Nyyssonen,
Lakka, & Salonen, 2000; von Schacky, Angerer, Kothny,
Theisen, & Mudra, 1999). The cardioprotective effects of
omega-3 fatty acids are ascribed to improvements in various cardiovascular risk factors including a reduction in
blood-platelet aggregation (Mori, Beilin, Burke, Morris,
& Ritchie, 1997; Phang, Sinclair, Linez, & Garg, 2012),
decreased inflammation (Heller, Koch, Schmeck, & van
Ackern, 1998; Zhao et al., 2004), enhanced endothelial
function (Fleischhauer, Yan & Fischell, 1993), positive
changes in blood lipids (Calabresi et al., 2004; Harris,
1989; Herrmann, Biermann, & Kostner, 1995), and
decreased blood pressure (Paschos, Magkos, Panagiotakos, Votteas, & Zampelas, 2007; Prasad, 2009).
EPA and DHA, derived from fish oil, can cause
dual inhibition of cyclo-oxygenase-2 and 5-lipoxygenase pathways for metabolism of arachidonic acid (AA).
EPA is a much less preferred substrate than AA for both
pathways and generally by substrate competition inhibits release of AA-derived eicosanoids, thus reducing
the generation of proinflammatory “tetraene” 4-series
leukotrienes and 2-series prostanoids and production
of cytokines from inflammatory cells (Mickleborough,
83
84 Mickleborough
2008). Consuming fish oil results in partial replacement
of AA in inflammatory-cell membranes by EPA and thus
demonstrates a potentially beneficial anti-inflammatory
effect of omega-3 PUFAs. Supplementing the diet with
omega-3 PUFAs has been shown to reduce AA concentrations in neutrophils, reduce neutrophil chemotaxis,
and reduce leukotriene generation (Lee et al., 1985). The
effects of omega-3 PUFAs on inflammatory cytokine gene
expression suggest that they modify the activity of the
transcription factors nuclear factor κ B and/or peroxisome
proliferator-activated receptor (PPAR)-γ (Calder, 2009).
Long-chain omega-3 PUFAs have not only been
shown to decrease the production of inflammatory
eicosanoids, cytokines, and reactive oxygen species but
also have been shown to possess immunomodulatory
effects (Calder, 2007). It appears that the EPA and DHA
membrane composition of immune cells can be altered
with long-term ingestion of omega-3 PUFAs, which can
influence phagocytosis, T-cell signaling, and antigenpresenting capabilities (Calder, 2007).
This review focuses on both human and animal
studies that assessed the effectiveness of omega-3
PUFA supplementation on the physiological response
to exercise. Few human studies, of which the results are
equivocal, have been conducted to assess the efficacy of
omega-3 PUFAs on inflammatory, immunomodulatory,
and subsequent exercise response in healthy individuals. However, studies evaluating the impact of omega-3
PUFA supplementation on exercise metabolism, muscle
damage, and endurance-exercise performance in animals
have yielded promising results. In addition, given the purported benefits of omega-3 PUFAs on the cardiovascular
system and carbohydrate fat and protein metabolism, it
has been hypothesized that supplementation with these
fatty acids may enhance the beneficial effects of physical activity, potentiating enhanced lipid oxidation and
improvements in exercise performance.
For this review, the keywords eicosapentaenoic
acid, docosahexaenoic acid, omega-3 PUFA, omega-6
PUFA, and fish oil were coupled with keywords exercise performance, physical performance, red blood cell
deformability, protein metabolism, inflammation, muscle
damage, exercise metabolism, exercise cardiac function,
blood flow, lipids, and migratory flight performance for
a MEDLINE, EMBASE, Cochrane Central Register of
Controlled Trials, Google Scholar, and SPORTDiscus
search.
Discussion
Omega-3 Fatty Acids
and Red Blood Cell Deformability
Red blood cell (RBC) deformability decreases with
exercise (Galea & Davidson, 1985; van der Brug, Peters,
Hardeman, Schep, & Mosterd, 1995) and is associated
with increased aggregation and transit time through
micropores (Simchon, Jan, & Chien, 1987; Yalcin, BorKueukatay, Senturk, & Baskurt, 2000), which may reduce
the efficacy of oxygen delivery through the microcirculation. RBC deformability refers to the cellular properties of
RBCs, which determine the degree of shape change under
a given level of applied force. RBCs can significantly
change their shape while passing through the microcirculation. RBC deformability is a measurable property,
and the preferred method for measuring deformability
is to use the ektacytometric principle, which is based on
laser-diffraction analysis (Baskurt et al., 2009). Briefly,
RBCs are exposed to increasing shear stress, and the laser
diffraction pattern through the suspension is recorded; it
goes from circular to elliptical as shear increases. From
these measurements, a deformability index for the cells
can be derived (Baskurt et al., 2009; Oostenbrug et al.,
1997).
A number of studies have shown that dietary fish oil
increases the deformability of RBCs as a consequence of
incorporation of omega-3 PUFAs into RBC membrane
phospholipids (Andersson, Nalsen, Tengblad, & Vessby,
2002; Cartwright, Pockley, Galloway, Greaves, & Preston, 1985; Terano et al., 1983). Omega-3 PUFAs have also
been shown to facilitate the transport of RBCs through
the capillary bed (Bruckner, Webb, Greenwell, Chow, &
Richardson, 1987), which could lead to enhanced oxygen
delivery to skeletal muscle and a subsequent improvement in exercise performance. In clinical studies, fish-oil
supplementation (2.8 g EPA/day for 3 months) enhanced
RBC deformability in patients with angina (Solomon et
al., 1990) and increased RBC deformability after supplementation of 1.8 g EPA and 1.2 g DHA/day for 4 months
in patients with claudication.
Several studies have investigated the effects of
fish-oil supplementation on RBC deformability and
subsequent exercise performance. Guezennec, Nadaud,
Satabin, Leger, and Lafargue (1989) evaluated the effect
of 6 g (1,080 mg EPA and 720 mg DHA) of fish-oil supplementation given daily over 6 weeks on RBC deformability after hypobaric exercise. Although the omega-3
PUFA was incorporated into the RBC membranes, this
inclusion did not result in a significant change in RBC
deformability at rest. The RBC phospholipid content
of EPA (20:5) and DHA (22:6), expressed as a weight
percentage of total fatty-acid content, was significantly
increased after fish-oil supplementation (EPA, 3.9% ±
0.30%; DHA, 6.40% ± 0.28%) compared with the control group (EPA, 1.8% + 0.22%; DHA, 4.28% + 0.15%).
However, after hypobaric exercise, RBC deformability
decreased less on than he fish-oil diet compared with
the normal diet. Guezennec et al. concluded that VO2max
increased and oxygen saturation decreased after 6 weeks
of fish-oil supplementation. However, the data from
that study are difficult to interpret since the same power
output, with an increased VO2max, was observed. Oostenbrug et al. (1997) investigated the effects of 3 weeks of
fish-oil supplementation (6 g/day) and vitamin E (300
IU/day) on RBC deformability and lipid peroxidation
in 24 trained cyclists. Exercise performance (1-hr time
trial) and RBC characteristics were not improved by
fish oil. Malaguti, Baldini, Angeloni, Biagi, and Hrelia
Omega-3 and Physical Performance 85
(2008) evaluated the role of a high-protein, low-calorie,
PUFA-enriched (3 g/day) diet and a Mediterranean diet
on anthropometrics, RBC fatty-acid composition, and
plasma antioxidant defenses among nonprofessional volleyball athletes. They found that total antioxidant activity
increased in both groups and that RBC-membrane PUFA
content increased and body-mass index and total body
fat (calculated using skinfold-based body-fat estimation)
were significantly reduced only in the fish-oil-supplemented group. There is some concern that incorporating
omega-3 PUFAs into cell membranes may increase the
potential for lipid peroxidation (Pedersen et al., 2003),
which is much more evident in athletes who undergo
high oxidative stress (Allard, Kurian, Aghdassi, Muggli,
& Royall, 1997). While it is clear that pharmaceuticalgrade fish oil leads to an increase in RBC-membrane
PUFA content and hence an improved hemorrheological
response in athletes, it is unclear if the pro-oxidant effects
of fish-oil supplementation could unfavorably affect these
benefits. It is possible that the balance between beneficial
and harmful effects of PUFAs depends on dose.
EPA has been shown to be incorporated more efficiently than DHA into RBC membranes (Gans et al.,
1990). An increased amount of PUFAs has been found in
the phospholipid membranes of RBCs in trained versus
untrained skeletal muscle (Andersson, Sjodin, Hedman,
Olsson, & Vessby, 2000; Helge et al., 2001). In Helge et
al.’s study (2001), 7 male subjects performed endurance
training of the knee extensors of one leg for 4 weeks. The
other leg served as a control. Before, after 4 days, and
after 4 weeks, muscle biopsies were obtained from the
vastus lateralis. After 4 weeks, the phospholipid fatty-acid
contents of oleic acid 18:1(n-9) and DHA 22:6(n-3) were
significantly higher in the trained (10.9% ± 0.5% and 3.2%
± 0.4% of total fatty acids, respectively) than the untrained
leg (8.8% ± 0.5% and 2.6% ± 0.4%). This discrepancy was
not explained by different fiber-type distribution alone but
appears to be a direct consequence of changes in fatty-acid
metabolism due to a higher level of physical activity. Diet
appears to have played a minimal role in Helge et al.’s
study, as dietary intake was similar on both legs
Omega-3 Fatty Acids, Muscle Damage,
and Inflammatory Response to Exercise
Consistent findings of elevated oxidative stress and
inflammatory responses in exercise-trained individuals
have been observed in athletes who engage in long-duration exercise such as marathon or triathlon competitions
(Fisher-Wellman & Bloomer, 2009). Chronic strenuous exercise itself has been demonstrated to promote
impaired immune function (Brenner, Shek, & Shephard,
1994). Intense exercise training leads to muscle fatigue,
soreness, dehydration, muscle structural damage, freeradical damage, lactic-acid build-up, neutrophilia, muscle
swelling, central-nervous-tissue fatigue, and catabolism
of nutrient stores (Armstrong, Warren, & Warren, 1991).
Inflammation is a physiological response to injury
or tissue damage that involves the immune system to
mediate local defenses. The inflammatory response is
characterized by increased expression of cytokines such
as tumor necrosis factor (TNF)-α, interleukin (IL)-1β,
and IL-6 (Northoff & Berg, 1991). Cytokines can trigger the release of acute-phase proteins and inflammatory mediators such as leukotrienes and prostaglandins.
Increases in oxidative stress after a bout of strenuous
exercise (Sen, 1995) are accompanied by a diminution in
natural immunity and decreased resistance to infection.
It has been shown that supplementation with 1.75 g/day
EPA and 1.05 g/day DHA for 3 weeks attenuates the rise
in acute-phase proteins occurring after exercise (Ernst,
Saradeth, & Achhammer, 1991) and stops postexercise
immunosuppression of the immunoglobulin M-plaqueforming response (Benquet et al., 1994). Tartibian,
Maleki, and Abbasi (2009) assessed the effect of 324
mg/day EPA and 216 mg/day DHA administered over
30 days before and during 48 hr after step training. The
control group (n = 9) received no supplement, while
the placebo group (n = 9) received a matching placebo
capsule. The omega-3 PUFA group (n = 9) also received
100 IU of d-α-tocopherol/dl-α-tocopherol acetate to
minimize long-chain unsaturated fatty-acid oxidation
(Sen et al., 1997). While no significant difference was
observed between groups for pain level of the lower limbs
and knee range of motion before, immediately after, and
24 hr after the exercise, a significant decrease in indirect
indices of delayed-onset muscle soreness (DOMS),
such as perceived pain, thigh circumference (indicator
of muscle swelling/inflammation), and range of motion,
and were seen 48 hr after exercise in the omega-3 PUFA
group compared with the placebo and control groups. In
contrast, Lenn et al. (2002) examined the effects of 1.8
g/day of fish oil and isoflavones on DOMS for 30 days
before and after 7 days of eccentric exercise and found
no significant effects of attenuated perceived pain. It is
possible that differences in the eccentric-exercise protocol
or the muscle groups that were studied contributed to the
differences in findings between the two studies (Lenn et
al., 2002; Tartibian et al., 2009).
Recently, Bloomer, Larson, Fisher-Wellman,
Galpin, and Schilling (2009) examined the efficacy of
EPA (2,224 mg/day) and DHA (2,208 mg/day) for 6
weeks on resting and exercise-induced inflammation,
oxidative stress, and aerobic exercise (60-min walk on
a treadmill while carrying a weighted backpack equal
to 25% of body mass). The treadmill speed and grade
were altered every 5 min to mimic the type and duration of exercise performed by the military in a typical
physical march. Bloomer et al. found that the EPA/DHA
supplementation significantly increased plasma levels of
these fatty acids and significantly reduced resting levels
of inflammatory biomarkers (i.e., C-reactive protein
and TNF-α) but did not have any significant effect on
exercise-induced inflammation or oxidative stress (i.e.,
total antioxidant capacity, protein carbonyls, malondialdehyde, hydrogen peroxide, xanthine oxidase, and nitric
oxide). They concluded that the latter finding may be due
to the fact that trained men exhibit minimal inflammation
86 Mickleborough
and oxidative-stress responses to moderate aerobic
exercise. There are a number of possible explanations
as to why Bloomer et al. did not observe an attenuation
of exercise-induced inflammation and oxidative stress on
the EPA/DHA-rich diet. It is possible that the exercise
protocol they chose was too low in intensity and duration
to promote significant oxidative stress and inflammation
in their sample of trained men. In addition, they chose
a protocol that was concentric in nature, and therefore
the amount of muscle damage (and subsequent related
reactive oxygen and nitrogen species) would be expected
to be minimal. This was confirmed by their finding of
insignificant increases in muscle soreness and creatine
kinase levels in the blood. Thus, their results may have
been different if they had used either an aerobic-exercise
bout involving an eccentric component (e.g., downhill
running) or a heavy-resistance-exercise protocol. Jouris,
McDaniel, and Weiss (2011) recently demonstrated that
2,000 mg EPA and 1,000 mg EPA taken daily over 7 days
reduced exercise-induced muscle soreness (i.e., using a
visual analog scale when “weighted”—while the participants flexed and extended their elbow while holding
a 1.1-kg weight—and when “fully extended”—participants attempted to fully extend their elbow) induced by
eccentric arm-curl exercise compared with baseline and
a control group (no supplement).
Toft et al. (2000) investigated whether 3.6 g/day of
fish-oil supplementation (53% EPA and 31% DHA) and
21.6 mg tocopherol taken for 6 weeks was able to reduce
the acute-phase response and increased cytokine release
associated with strenuous exercise in 20 endurancetrained men. While they found that strenuous exercise
(marathon running) did increase plasma levels of TNF-α,
IL-6, IL-1ra, and transforming growth factor-β1, fishoil supplementation did not affect the exercise-induced
cytokine increase, despite incorporation of omega-3
PUFA into blood mononuclear cell plasma membranes.
In contrast, Andrade, Ribeiro, Bozza, Costa Rosa, and
Tavares do Carmo (2007) found that 6 weeks of 1.8-g/
day fish-oil supplementation (950 mg EPA and 500 mg
DHA) given to elite swimmers during a period of intense
training significantly increased plasma levels of EPA
and DHA and significantly reduced plasma levels of AA
compared with their placebo group. In addition, the fishoil-supplemented group exhibited significant reductions
in prostaglandin E2, interferon-γ, and TNF-α and a significant increase in IL-2. It is important to note that both
IL-2 and interferon-γ are important in the establishment
of balance of the TH1/TH2 response, and thus Andrade
et al.’s findings are important since the data indicate that
fish-oil supplementation can influence immune responses
in elite swimmers during periods of intense training.
Whether these findings translate into improved exercise
performance has yet to be studied.
Poprzecki, Zajac, Chalimoniuk, Waskiewicz, and
Langfort (2009) recently sought to elucidate whether a
low dose of omega-3 PUFA and exercise could enhance
blood antioxidant status and influence blood plasma
lipid profile. They found that 6 weeks of a low dose of
n-3 PUFA (1.3 g/day; 30% EPA, 20% DHA, and 4 mg
α-tocopherol) in untrained healthy subjects partially
protected against the reduced superoxide dismutase in
response to acute endurance exercise (1 hr of cycling
exercise at 60% VO2max) and increased catalase activity
during recovery periods compared with placebo. Furthermore, they found that omega-3 PUFA supplementation
did not significantly alter oxygen consumption during
exercise or the blood plasma lipid profile compared
with placebo. They concluded that the beneficial effect
of omega-3 PUFA supplementation during endurance
exercise may be attributable to the activation of the
superoxide dismutase and catalase pathways. On the other
hand, Filaire et al. (2011) recently showed that 6 weeks
of daily supplementation with 600 mg EPA and 400 mg
DHA increased oxidative stress at baseline in trained
men and did not attenuate the increased oxidative stress
resulting from exercise (cycling exercise to exhaustion).
Addition of antioxidants (30 mg vitamin E, 60 mg vitamin
C, and 6 mg β-carotene) to the diet did not prevent the
formation of oxidation products at rest. On the contrary,
the combination of antioxidants added to the omega-3
PUFA supplement led to a decrease in malondialdehyde
and lipoperoxide concentrations, maximal rate of oxidation during the propagating chain reaction, and the
maximum amount of conjugated dienes accumulated after
the propagation phase following a judo training session.
Given the antagonistic effects of n-3 PUFAs on proinflammatory eicosanoids (Calder, 2006), supplementation may help alleviate DOMS, which could indirectly
benefit exercise performance. In addition, positive effects
on DOMS may be augmented by the ability of n-3 PUFAs
to increase blood flow (Stebbins, Hammel, Marshal,
Spangenberg, & Musch, 2010; Walser, Giordano, &
Stebbins, 2006), thereby aiding in a more rapid nutrient delivery postexercise. However, further studies are
needed to determine whether n-3 PUFAs may, in fact,
produce analgesic effects.
Omega-3 Fatty Acids
and Exercise Metabolism
During high-intensity exercise, hepatic glucose production (HGP) and glucose utilization are stimulated to
prevent hypoglycemia (Trimmer et al., 2002). Endurance
training leads to increased fat and decreased carbohydrate
oxidation, which is concomitant with a reduction in
HGP (Coggan, Kohrt, Spina, Bier, & Holloszy, 1990).
Puhakainen, Ahola, and Yki-Jarvinen (1995) observed
enhanced gluconeogenesis without increased HGP in
9 obese patients with Type II diabetes who consumed
fish-oil supplements (12 g/day). Delarue, Labarthe, and
Cohen (2003) examined the effect of 3 weeks of fish-oil
supplementation (6 g/day) and exercise on plasma glucose disappearance and HGP in 6 untrained males. At rest,
HGP and plasma glucose disappearance were unchanged
in the fish-oil-supplementation group compared with the
control group. However, during the two 90-min cycling
bouts (60% of VO2max) the fish-oil-supplemented group
Omega-3 and Physical Performance 87
demonstrated a reduced plasma glucose-disappearance
rate and a reduced HGP, by 26% and 21%, respectively,
and reduced glucose metabolic clearance rate compared
with the exercise controls. In addition, after exercise,
lipid oxidation was enhanced and carbohydrate oxidation
decreased after fish-oil supplementation, supporting the
assumption that fish oil may reduce the glucose metabolic
clearance rate by facilitating fat oxidation.
Endurance training and/or a fish-oil-supplemented
diet can affect cytoplasmic fatty-acid-binding protein
(FABP[c]) content in rat skeletal muscles and heart
(Clavel, Farout, Briand, Briand, & Jouanel, 2002). After
8 weeks of swimming, 34 trained rats exhibited higher
FABP(c) content in the extensor digitorum longus and
in the gastrocnemius than did the 32 control rats. The
FABP(c) increase was associated with an increase of
citrate synthase activity (85% and 93%, respectively, in
the two muscles), whereas lactate dehydrogenase activity
decreased significantly. Therefore, increasing oxidative
capacities of muscle by exercise resulted in a concomitant
increase of the FABP(c) content. Giving an omega-3
PUFA-supplemented diet for 8 weeks induced a large
rise of the FABP(c) in extensor digitorum longus (300%),
gastrocnemius (250%), soleus (50%), and heart (15%)
without a concurrent accumulation of intramuscular
triglycerides or modification of citrate synthase activity.
These results suggest that omega-3 PUFAs may increase
FABP(c) content by up-regulating fatty-acid metabolism
genes via PPAR-α activation. Endurance-trained rats fed
with the omega-3 PUFA-rich diet had similar FABP(c)
content in the gastrocnemius muscle compared with
sedentary omega-3 PUFA-fed rats, whereas an additive
effect of exercise and diet was observed in the extensor digitorum longus. As a result, both exercise and the
omega-3 PUFA-enriched diet influenced FABP(c) content
in muscle. These two physiological treatments presumably acted on FABP(c) content by increasing fatty-acid
flux within the cell (Clavel et al., 2002). The shift toward
a greater use of fat reduces the rate of glycogen depletion
and thus fatigue.
Since both n-3 and n-9 PUFA may increase fat oxidation, Boss, Lecoultre, Ruffieux, Tappy, and Schneiter
(2010) recently evaluated the combined effects of endurance training and these unsaturated fatty acids on physical performance, fat oxidation, and insulin sensitivity
in 16 sedentary male subjects. Subjects were randomly
assigned to either an isoenergetic diet with fish oils and
olive oils (52% unsaturated fatty acids [UFA], 12% SFA,
6% monounsaturated fatty acids [MUFA], 5% PUFA,
14% protein) or a control diet and underwent a 10-day
gradual endurance-training program. While training
significantly increased time to exhaustion during cycling
exercise at 80% VO2max and improved insulin sensitivity,
these effects were not different between groups (UFA and
control). In addition, there was no difference in VO2max or
fat oxidation between groups. Boss et al. concluded that
a diet enriched with fish and olive oil does not enhance
the effects of a short-term endurance-training protocol in
healthy young subjects. A major weakness in that study
is that the effects of the UFA on lipid oxidation may have
passed undetected due to the small sample size and thus
low statistical power. In addition, both groups differed
in the amount of PUFA (EPA and DHA) and MUFA
(oleate), making it impossible to assign specific effects
to either type of fat.
Omega-3 PUFAs are professed to act as metabolic
fuel partitioners (Clarke, 2001), up-regulating lipid
oxidative enzymes and down-regulating lipogenic gene
expression (Jump, Clarke, Thelen, & Liimatta, 1994).
This is partly due to the ability of n-3 PUFAs to bind
and activate various isoforms of the PPAR (Lin, Ruuska,
Shaw, Dong, & Noy, 1999). Although the mechanism by
which omega-3 PUFAs activate PPAR-α remain elusive,
the oxidized linoleate and arachidonate metabolites
13-hydroxy-9Z,11E-octadecadienoic acid, 15-hydroxy5Z,8Z,11Z,13E-eicosatetraenoic acid, prostaglandin J2,
and 15-deoxy-d′12,14-prostaglandin J2 are generally
believed to be natural PPAR ligands (Bell-Parikh et al.,
2003; Ide, Egan, Bell-Parikh, & FitzGerald, 2003). Thus,
it is likely that oxidative derivatives of omega-3 PUFAs,
and their eicosanoid products, bind PPARs (Mishra,
Chaudhary, & Sethi, 2004). Hostetler, Petrescu, Kier, and
Schroeder (2005) demonstrated that omega-3 PUFAs, as
well as their coenzyme A derivatives, but not saturated
fatty acids, can directly bind to PPARs. Specifically, the
PPAR-α isoform has been shown to play an important
role in managing glucose and fatty-acid homeostasis (Su
& Jones, 1993), including the expression of numerous
gene-encoding proteins involved in lipid transport and
oxidation, including hepatic carnitine acyltransferase
and hepatic and skeletal-muscle peroxisomal acyl-CoA
oxidase (Clarke & Jump, 1997). Putatively, increased
PPAR-α should allow a greater reliance on fat for fuel
during exercise, while sparing muscle glycogen and
improving both body composition and exercise performance.
Several studies have shown that n-3 PUFA supplementation results in greater accretion of muscle proteins
in both humans (Neschen et al., 2007; Robinson &
Stone, 2006; Schoeller, 1995) and animals (Bergeron,
Julien, Davis, Myre, & Thivierge, 2007; Gingras et al.,
2007). In addition, n-3 PUFAs may enhance mTOR/
p70s6k signaling (Schoeller, 1995), a pathway thought be
involved in decreasing proteolysis by down-regulating the
ubiquitin-proteasome pathway (Warner, Ullrich, Albrink,
& Yeater, 1989), which in conjunction with elevated
protein synthesis would result in an even greater accretion of muscle proteins. However, it should be noted that
none of these studies were performed in conjunction with
exercise. Therefore, further research is required to examine whether n-3 PUFA supplementation may potentiate
gains in lean muscle mass when combined with exercise.
Omega-3 Fatty Acids
and Human Physical Performance
A limited number of human studies have been performed
directly examining the influence of omega-3 PUFA
88 Mickleborough
supplementation on exercise performance in healthy subjects. Brilla and Landerholm (1990) examined the effects
of fish-oil feeding and exercise training in 32 sedentary
males. The subjects were supplemented with omega-3
PUFA (4 g/day) and exercised three times per week for 10
weeks. Both the omega-3 PUFA-supplemented exercised
and nonexercised groups exhibited an increased aerobic
ventilatory threshold compared with controls. Whereas
exercise training resulted in an increased VO2max, fish-oil
supplementation had no effect on VO2max. Similarly, in a
study (Raastad, Hostmark, & Stromme, 1997) performed
in well-trained soccer players, omega-3 PUFA (1.6 g/day
EPA and 1.04 g/day DHA) had no effect on aerobic power
or running performance when they followed their normal
training regimens. However, the athletes displayed significantly lower triacylglycerol levels after supplementation.
It has been hypothesized that this attenuation in plasma
triacylglycerol levels is caused by decreased lipoprotein
triacylglycerol secretion and inhibited triacylglycerol
synthesis. Huffman, Altena, Mawhinney, and Thomas
(2004) reported a trend for improvement in exercise time
to volitional fatigue (after jogging for 75 min at 60%
VO2max) after 4 g/day (300 mg EPA and 200 mg DHA)
of fish oil administered over 4 weeks.
Buckley, Burgess, Murphy, and Howe (2009) recently
examined the effects of 5 weeks of omega-3 PUFA (0.36
g/day EPA and 1.56 g/day DHA) supplementation on
endurance performance, recovery, and cardiovascular
risk factors in elite Australian Rules football players. The
data indicated that on the omega-3 PUFA-supplemented
diet RBCs’ omega-3 PUFA content doubled from
baseline and serum triglycerides and heart rate during
submaximal exercise were reduced, but no improvement
in endurance-exercise performance or recovery was
observed. The authors concluded that omega-3 PUFA
supplementation improved cardiovascular efficiency
during submaximal exercise, which may assist with the
sustained performance of submaximal exercise. Walser
and Stebbins (2008) showed that 3 g/day EPA and 2 g/day
DHA taken over 6 weeks enhanced stroke volume and
cardiac output responses to moderate-intensity exercise
and tended to augment systemic vascular resistance (in 9
of 12 healthy subjects). They speculated that these effects
may be due to attenuation of sympathetically induced
vasoconstriction and/or augmentation of vasodilatation
in skeletal muscle during exercise, and thus the findings
have implications for enhancing oxygen delivery during
exercise and improving functional capacity.
Recently, Nieman, Henson, McAnulty, Jin, and
Maxwell (2009) investigated the efficacy of 2.4 g (2 g/
day EPA and 0.4 g/day DHA) of fish-oil supplementation
over 6 weeks on exercise performance, inflammation, and
immune measures in 23 trained cyclists before and after
a 3-day period of intense exercise. While a significant
increase in plasma EPA and DHA was observed, no
changes after 6 weeks of fish-oil supplementation were
seen in inflammatory measures (IL-1ra, IL-6, and IL-8),
immune measures (blood leukocytes, C-reactive protein,
creatine kinase, salivary-IgA, and myeloperoxidase), or
10-km time-trial performance (~65% of maximum power
output). Nieman et al. employed a more robust research
design than many of the studies examining the influence
of fish-oil supplementation on inflammatory and immune
measures and exercise performance. However, there are
a few possible explanations for the negative outcomes
of their study. First, it is highly unlikely that the 3 days
of intensified training (cycling) induced a sufficiently
high oxidative and inflammatory stress, and, second,
the dosage of fish oil used is low compared with other
studies (Huffman et al., 2004; Mickleborough, Lindley,
Ionescu, & Fly, 2006; Mickleborough, Murray, Ionescu,
& Lindley, 2003; Walser & Stebbins, 2008). In a followup study, McAnulty et al. (2010) showed that omega-3
PUFA supplementation was associated with an increase
in F2-isoprostanes in response to heavy cycling exercise
and that supplementation with antioxidant vitamins and
minerals does attenuate the increase in F2-isoprostanes
but does not increase ferric-reducing antioxidant potential. Based on these data it is quite clear that further
research is required on whether the potential benefits of
omega-3 PUFA supplementation outweigh the potential
risks of enhanced lipid peroxidation in athletes engaged
in heavy exercise.
While, at present, the limited human data do not
support the hypothesis that omega-3 PUFA supplementation is effective in enhancing exercise performance, it
has been demonstrated that omega-3 PUFA can affect
not only cognitive function but also mood and emotional
states (e.g., depression) and may act as a mood stabilizer
(Fontani et al., 2005; Silvers & Scott, 2002). Guzman,
Esteve, Pablos, Pablos, and Villegas (2011) recently
showed that supplementing 24 female elite soccer players
with 3.5 g/day of DHA-rich fish oil for 4 weeks produced
perceptual-motor benefits (i.e., improvements in complex
reaction time and efficiency), which supports the view
that DHA may improve performance in sports where
perceptual motor activity and decision making are the
keys to success (Overney, Blanke, & Herzog, 2008). For
example, omega-3 PUFAs may have potential to enhance
the decision-making abilities of athletes who engage in
sports performed in extreme and stressful environmental
conditions (e.g., altitude, extreme heat or cold)
Omega-3 Fatty Acids
and Exercising Cardiac Function
In a meta-analysis of randomized, double-blind, placebocontrolled human trials, fish-oil supplementation reduced
heart rate at rest by 1.6 beats/min (Mozaffarian et al.,
2005). This finding in humans confirms experimental
studies conducted in isolated rat myocytes, exercising
dogs, and nonhuman primates that also suggest that fish
oil may have direct cardiac electrophysiological effects
including the slowing of heart rate (Billman, Kang, &
Leaf, 1997; Leaf, Kang, Xiao, & Billman, 2003; McLennan, 2001). Potential mechanisms such as effects on the
sinus node, ventricular efficiency, or autonomic function
warrant further investigation. To date there have only been
Omega-3 and Physical Performance 89
a few studies conducted examining the effect of fish-oil
supplementation on cardiac function during exercise.
Peoples, McLennan, Howe, and Groeller (2008)
examined the effects of fish-oil supplementation (8 × 1-g
capsules/day of omega-3 PUFA-rich tuna oil or placebo
for 8 weeks) on human heart function in well-trained
males and found that during exercise (55% of VO2max
until voluntary exhaustion) they exhibited significantly
lower heart rates, rate pressure product, and whole-body
O2-consumption than with placebo. However, a limitation
in their study is the lack of a measure of exercise performance. Ninio, Hill, Howe, Buckley, and Saint (2008)
showed that intake of 0.36 g/day of EPA and 1.56 g/day
of DHA increased parasympathetic measures of heartrate variability and lowered the heart-rate response to
exercise in patients with risk factors for coronary artery
disease. That study provides further evidence supporting
the use of fish-oil supplementation not only for patients
with established coronary disease but also for those at
risk for future cardiovascular disease.
Walser et al. (2006) showed that fish-oil supplementation (3.0 g/day EPA and 2.0 g/day DHA) enhances
exercise-induced increases in brachial-artery diameter
and blood flow during rhythmic handgrip exercise. They
speculated that these findings may have implications for
patients with cardiovascular disease and exercise intolerance. In a follow-up study, Stebbins et al. (2010) showed
that supplementation with EPA and DHA can augment
the contraction-induced increases in skeletal-muscle
blood flow and conductance in exercising rats, therefore
resulting in strong correlations between changes in these
two variables and the percent sum oxidative fibers (Types
I and IIa) observed in the individual muscles or muscle
parts. These augmentations in blood flow and conductance occurred in the absence of any changes in perfusion pressure (i.e., mean arterial pressure) or heart rate.
These data indicate that EPA and DHA supplementation
may effectively alter vasoreactivity in the vasculature of
skeletal muscle. Stebbins et al. speculated that the source
of this enhanced skeletal-muscle blood flow is increased
cardiac output caused by a decrease in systemic vascular resistance that is concomitant with PUFA-induced
increases in muscle conductance.
Omega-3 Fatty Acids
and Exercising Animals: Relevance
to Human Exercise Performance
Several previous studies suggested that intake of PUFAs
may indeed affect the performance of skeletal muscles
and locomotion in vertebrates. In Atlantic salmon, for
instance, dietary fatty-acid composition and resulting
changes in muscle lipid composition significantly affected
maximum swimming speed. These effects were largely
due to a positive relation between swimming speed and
the most common omega-6 fatty acid in muscle lipids,
linoleic acid (Mckenzie, Higg, Dosanjh, Deacon, &
Randell, 1998). Salmon fed a diet in which menhaden
oil furnished the entire supplemental lipid had a sig-
nificantly lower swimming speed than those fed a diet
in which the supplemental lipid was an equal blend of
menhaden and canola oil (rich in 18-carbon unsaturated
fatty acids). Furthermore, there was a highly significant
linear relationship between dietary and/or muscle levels
of particular fatty acids or groups of fatty acids and swimming speed (Mckenzie et al., 1998).
In addition, muscles that undergo very high contraction frequencies, such as the pectoral muscle in
hummingbirds, contain very large amounts of DHA
(Infante, Kirwan, & Brenna, 2001). In humans, training
exercise increases muscle PUFA content (Helge et al.,
2001). Furthermore, it has recently been found that the
proportions of PUFA in the muscle phospholipids of an
extremely fast runner, the brown hare (Lepus europaeus),
are very high compared with other mammals (Valencak,
Arnold, Tataruch, & Ruf, 2003). Based on these findings,
Ruf, Valencak, Tataruch, and Arnold (2006) hypothesized
that muscle phospholipid profiles may be functionally
related to locomotor performance. Their study examined
the relationship between total PUFA content, any of the
PUFA subclasses, or a particular fatty acid and locomotor
function as measured by running speed of 36 mammalian
species. The data revealed a strong relationship between
the omega-6 PUFA content in muscle phospholipids
and maximum running speed in mammals. Ruf et al.
speculated that omega-6 PUFAs exert a positive effect
on muscle performance and maximum running speed by
facilitating Ca2+ uptake into the sarcoplasmic reticulum
by increasing the activity of sarcoplasmic Ca2+ Mg2+ATPase (Ushio et al., 1997).
Lortet and Verger (1995) investigated the cardiac
function of anesthetized rats after the administration
of three different diets enriched in saturated oil (lard),
omega-6 PUFA (sunflower oil), or omega-3 PUFA (fish
oil) at baseline and after a moderate sustained exercise bout. The animals who consumed the fish-oil diet
exhibited changes in hemodynamic parameters (20%
reduction in left-ventricular pressure, maximal rate of
rise in pressure [LVdP/dtmax], mean aortic pressure, and
heart rate and a 30% reduction in LVdP/dtmin) compared
with the animals who consumed the other diets, but only
when they participated in the moderate exercise-running
protocol. Lortet and Verger speculated that the increased
production of endothelium-derived relaxation factor and/
or a decrease in blood viscosity could explain their results.
Demaison, Blet, Sergiel, Gregoire, and Argaud (2000)
found that rats consuming fish oil had reduced heart
rate, aortic flow, and cardiac output due to a decrease in
vascular resistance. Similarly, O’Connor et al. (2004)
found that thoroughbred horses administered fish oil for
63 days had lower heart rates and packed-cell volume
during exercise than horses fed corn oil.
The endurance capacity of long-distance migrants
has fascinated scientists for many years. Recent work
has attempted to unravel the physiological mechanisms
that underlie their athletic performance. Because of
their extreme athletic accomplishments, migrant birds
have recently received attention as models for studying
90 Mickleborough
the effects of dietary PUFAs on exercise (Price, 2010).
Modern tracking using satellite technology has shown
that annual round-trip flights of more than 64,000 km
are not uncommon in some marine birds (Shaffer et al.,
2006). The activities of marker enzymes for flux capacity through the citric acid and β-oxidation cycle have
been measured in several species of migrant birds. As
anticipated, the oxidative capacity of their flight muscles
is higher than that of sedentary species (Bishop, Butler,
Egginton, el Haj, & Gabrielsen, 1995; Suarez et al.,
1990), and it is further enhanced seasonally at the time
of migration (Guglielmo, Haunerland, Hochachka, &
Williams, 2002; Maillet & Weber, 2007).
Recent research reveals that some migrant birds
use components of their diet as performance-enhancing
substances to achieve a large increase in aerobic capacity
just before departure. This form of “natural doping” was
discovered in semipalmated sandpipers (Calidris pusilla
L.) preparing for the longest nonstop flight of their annual
cycle, which is an approximately 4,500-km transatlantic
trip from eastern Canada to South America requiring a
3-day flight at approximately 60 km/hr (Guglielmo et
al., 2002; Maillet & Weber, 2006, 2007). While refueling
in the Bay of Fundy (New Brunswick, Canada), these
sandpipers double their body mass from approximately
20 to 40 g by feeding on small burrowing amphipods
(Corophium volutator Pallas) that contain very high levels
of omega-3 PUFAs. This activity is noteworthy since
the fatty-acid composition of artificial diets has been
shown to influence the capacity for endurance exercise
in a variety of animals including rats (Ayre & Hulbert,
1997), Atlantic salmon (Salmo salar L.; Mckenzie et
al., 1998), and the red-eyed vireo (Vireo olivaceus L.), a
migrant songbird (Pierce, McWilliams, O’Connor, Place,
& Guglielmo, 2005).
EPA and DHA account for 45% of total lipids
in the diet naturally consumed by the semipalmated
sandpiper. Therefore, it seems these birds enhance the
aerobic capacity of their flight muscle by eating large
amounts of omega-3 PUFAs that are known to cause
pharmacological-like effects in mammalian cells in vitro.
While the exact molecular mechanisms are unknown,
natural doping appears to be mediated by at least two
processes: the incorporation of dietary omega-3 PUFAs
into the membrane phospholipids and their binding
to nuclear receptors such as PPARs that regulate the
expression of genes controlling fundamental aspects
of lipid metabolism (Nagahuedi, Popesku, Trudeau, &
Weber, 2009). Maillet and Weber (2007) found that the
oxidative enzymes (citrate synthase [Kreb’s cycle] and
3-hydroxyacyl dehydrogenase [β-oxidation]) were significantly increased in the flight muscles of semipalmated
sandpipers while refueling on amphipods (Corophium)
rich in omega-3 PUFA. They also found that the activities
of the enzymes were correlated with the omega-3 PUFA
content in phospholipids. The semipalmated sandpiper is
the first documented case of a long-distance migrant using
natural doping to prime its locomotor muscles for endurance exercise (Maillet & Weber, 2006, 2007). High lipid
fluxes are made possible by lipoprotein shuttles, by high
concentrations of FABP that accelerate lipid transport,
and by boosting the metabolic machinery for lipolysis in
adipocytes and lipid oxidation in muscle mitochondria.
Research on the physiology of long-distance migrants
may have important implications for the not only treatment of obesity but also for improving the performance
of human athletes.
Conclusion
While a number of studies have assessed the efficacy of
omega-3 PUFA supplementation on RBC deformability,
muscle damage, inflammation, and metabolism during
exercise, there are only a limited number that evaluated the impact of omega-3 PUFA supplementation on
exercise performance. This review has shown that, at
present, the human data are inconclusive as to whether
omega-3 PUFA supplementation is effective in attenuating the inflammatory and immunomodulatory response to
exercise and thus could enhance subsequent exercise performance. It is clear that further studies are needed to provide unequivocal proof of this effect. The inconsistency
among study results may be due to the heterogeneity in
(a) definitions of setting (field vs. laboratory test), mode,
intensity, and duration of the exercise test used to assess
performance; (b) definitions of populations (e.g., age,
gender, untrained vs. trained individuals); (c) interventions and their contrasts with comparators (e.g., different
types and amounts of fish oil and omega-3 PUFAs used);
(d) the dosage and duration of omega-3 PUFA-supplementation variation among published studies; and (e) the
timing of the measurements and selection of biomarkers
among studies. Future studies investigating the efficacy
of omega-3 PUFA supplementation in exercise-trained
individuals should consider using an exercise protocol of
sufficient duration and intensity to produce a more robust
oxidative and inflammatory response.
However, animal studies assessing the effectiveness
of omega-3 PUFA supplementation on exercise metabolism and endurance exercise performance have produced
very promising findings. Based on the current literature,
future studies in humans should focus on assessing the
effectiveness of omega-3 PUFA supplementation on
DOMS and subsequent exercise performance in athletes
(e.g., multisport) and military personnel who typically
engage in more than one workout per day using a more
robust research design than those that have been used in
previous studies. In addition, based on data generated
from long-distance migrant birds (Maillet & Weber,
2006, 2007), it would be of interest to assess the impact
of omega-3 PUFA supplementation on exercise metabolism and endurance exercise in untrained versus trained
individuals.
While the use of supplemental omega-3 PUFAs has
been indicated to improve performance in laboratory animals and migrant birds, and to a limited extent in humans,
it has not been definitely proven, and thus, at the present
time, it is difficult to make any firm recommendations to
athletes regarding the amount and duration of omega-3
Omega-3 and Physical Performance 91
PUFA supplementation. The reported health risks of
fish-oil supplementation are the following:
• Some species of fish are known to be contaminated
with toxins such as heavy metals, dioxins, and PCBs.
Fish-oil supplements are made from these fish and
may retain these contaminants unless they have
undergone molecular distillation to purify them.
Most studies that have looked at reputable brands of
fish-oil supplements have not found significant levels
of contamination. Pharmaceutical-grade fish oils
should be free of these contaminants (Kris-Etherton,
Grieger, & Etherton, 2009).
• One potential side effect of fish-oil supplements is an
increased risk of bleeding and immunosuppression
(Meydani et al., 1991; Ryan et al., 2009). Because
fish oils decrease the stickiness of blood platelets,
they decrease clot formation and can increase the
tendency to bleed. This is unlikely to be a problem
at low doses, but there is some evidence that high
doses may increase the risk of hemorrhagic stroke
(Kris-Etherton, Harris, & Appel, 2002).
• Fish oils are known to cause a variety of digestive
problems including flatulence, bloating, acid reflux,
nausea, and diarrhea (Kris-Etherton et al., 2002).
This can sometimes be prevented by taking fish-oil
supplements with meals and starting with a low dose.
• Although fish oils have been shown to lower triglyceride levels, as well as protect against heart disease,
higher doses may increase LDL cholesterol by up
to 10% (Kris-Etherton et al., 2002). However, more
research needs to be conducted in this area.
• Fish-oil supplements have been demonstrated to
lower blood pressure, which could be a problem for
individuals who already have low blood pressure
(Mori & Beilin, 2001).
• Some individuals have reported a “fishy taste” in
their mouth after taking fish-oil supplements (KrisEtherton et al., 2002).
Attempts should be made to establish an optimal
omega-3 PUFA dosage to maximize the risk-to-reward
ratio of supplementation. It has been suggested that for
most athletes, ingesting approximately 1–2 g/day of
EPA and DHA at a ratio of EPA to DHA of 2:1 would be
beneficial in counteracting exercise-induced inflammation and for the overall health of an athlete (Simopoulos,
2007). However, it should be noted that an omega-3 PUFA
(EPA+DHA) dose of ≤3,000 mg/day has been designated
as safe for general consumption by the U.S. Food and
Drug Administration (2004), and it is recommended that
athletes abide by this recommendation if consuming fish
oil to decrease muscle soreness or pain from exercise.
References
Albert, C.M., Campos, H., Stampfer, M.J., Ridker, P.M.,
Manson, J.E., Willett, W.C., & Ma, J. (2002). Blood levels
of long-chain n-3 fatty acids and the risk of sudden death.
The New England Journal of Medicine, 346, 1113–1118.
PubMed doi:10.1056/NEJMoa012918
Allard, J.P., Kurian, R., Aghdassi, E., Muggli, R., & Royall, D.
(1997). Lipid peroxidation during n-3 fatty acid and vitamin E supplementation in humans. Lipids, 32, 535–541.
PubMed doi:10.1007/s11745-997-0068-2
Andersson, A., Nalsen, C., Tengblad, S., & Vessby, B. (2002).
Fatty acid composition of skeletal muscle reflects dietary
fat composition in humans. The American Journal of
Clinical Nutrition, 76, 1222–1229. PubMed
Andersson, A., Sjodin, A., Hedman, A., Olsson, R., & Vessby,
B. (2000). Fatty acid profile of skeletal muscle phospholipids in trained and untrained young men. American
Journal of Physiology. Endocrinology and Metabolism,
279, E744–E751. PubMed
Andrade, P.M., Ribeiro, B.G., Bozza, M.T., Costa Rosa, L.F.,
& Tavares do Carmo, M.G. (2007). Effects of the fishoil supplementation on the immune and inflammatory
responses in elite swimmers. Prostaglandins, Leukotrienes, and Essential Fatty Acids, 77, 139–145. PubMed
doi:10.1016/j.plefa.2007.08.010
Armstrong, R.B., Warren, G.L., & Warren, J.A. (1991).
Mechanisms of exercise-induced muscle fibre injury.
Sports Medicine (Auckland, N.Z.), 12, 184–207. PubMed
doi:10.2165/00007256-199112030-00004
Ayre, K.J., & Hulbert, A.J. (1997). Dietary fatty acid profile
affects endurance in rats. Lipids, 32, 1265–1270. PubMed
doi:10.1007/s11745-006-0162-5
Baskurt, O.K., Hardeman, M.R., Uyuklu, M., Ulker, P., Cengiz,
M., Nemeth, N., . . . Meiselman, H.J. (2009). Comparison
of three commercially available ektacytometers with different shearing geometries. Biorheology, 46, 251–264.
PubMed
Bell-Parikh, L.C., Ide, T., Lawson, J.A., McNamara, P., Reilly,
M., & FitzGerald, G.A. (2003). Biosynthesis of 15-deoxydelta12,14-PGJ2 and the ligation of PPARγ. The Journal
of Clinical Investigation, 112, 945–955. PubMed
Benquet, C., Krzystyniak, K., Savard, R., Guertin, F., Oth, D.,
& Fournier, M. (1994). Modulation of exercise-induced
immunosuppression by dietary polyunsaturated fatty acids
in mice. Journal of Toxicology and Environmental Health,
43, 225–237. PubMed doi:10.1080/15287399409531917
Bergeron, K., Julien, P., Davis, T.A., Myre, A., & Thivierge,
M.C. (2007). Long-chain n-3 fatty acids enhance neonatal
insulin-regulated protein metabolism in piglets by differentially altering muscle lipid composition. Journal of
Lipid Research, 48, 2396–2410. PubMed doi:10.1194/jlr.
M700166-JLR200
Billman, G.E., Kang, J.X., & Leaf, A. (1997). Prevention of
ischemia-induced cardiac sudden death by n-3 polyunsaturated fatty acids in dogs. Lipids, 32, 1161–1168. PubMed
doi:10.1007/s11745-997-0149-2
Bishop, C.M., Butler, P.J., Egginton, S., el Haj, A.J., & Gabrielsen, G.W. (1995). Development of metabolic enzyme
activity in locomotor and cardiac muscles of the migratory
barnacle goose. The American Journal of Physiology, 269,
R64–R72. PubMed
Bloomer, R.J., Larson, D.E., Fisher-Wellman, K.H., Galpin,
A.J., & Schilling, B.K. (2009). Effect of eicosapentaenoic and docosahexaenoic acid on resting and exercise-
92 Mickleborough
induced inflammatory and oxidative stress biomarkers: A
randomized, placebo controlled, cross-over study. Lipids
in Health and Disease, 8, 36. PubMed doi:10.1186/1476511X-8-36
Boss, A., Lecoultre, V., Ruffieux, C., Tappy, L., & Schneiter,
P. (2010). Combined effects of endurance training and
dietary unsaturated fatty acids on physical performance,
fat oxidation and insulin sensitivity. The British Journal
of Nutrition, 103, 1151–1159. PubMed
Brenner, I.K., Shek, P.N., & Shephard, R.J. (1994). Infection
in athletes. Sports Medicine (Auckland, N.Z.), 17, 86–107.
PubMed doi:10.2165/00007256-199417020-00002
Brilla, L.R., & Landerholm, T.E. (1990). Effect of fish oil
supplementation and exercise on serum lipids and aerobic
fitness. Journal of Sports Medicine and Physical Fitness,
30, 173–180. PubMed
Bruckner, G., Webb, P., Greenwell, L., Chow, C., & Richardson,
D. (1987). Fish oil increases peripheral capillary blood cell
velocity in humans. Atherosclerosis, 66, 237–245. PubMed
doi:10.1016/0021-9150(87)90067-0
Buckley, J.D., Burgess, S., Murphy, K.J., & Howe, P.R. (2009).
DHA-rich fish oil lowers heart rate during submaximal
exercise in elite Australian Rules footballers. Journal of
Science and Medicine in Sport, 12, 503–507. PubMed
doi:10.1016/j.jsams.2008.01.011
Calabresi, L., Villa, B., Canavesi, M., Sirtori, C.R., James,
R.W., Bernini, F., & Franceschini, G. (2004). An omega-3
polyunsaturated fatty acid concentrate increases plasma
high-density lipoprotein 2 cholesterol and paraoxonase
levels in patients with familial combined hyperlipidemia.
Metabolism: Clinical and Experimental, 53, 153–158.
PubMed doi:10.1016/j.metabol.2003.09.007
Calder, P.C. (2006). n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. The American Journal of
Clinical Nutrition, 83, 1505S–1519S. PubMed
Calder, P.C. (2007). Immunomodulation by omega-3 fatty acids.
Prostaglandins, Leukotrienes, and Essential Fatty Acids,
77, 327–335. PubMed doi:10.1016/j.plefa.2007.10.015
Calder, P.C. (2009). Polyunsaturated fatty acids and inflammatory processes: New twists in an old tale. Biochimie,
91, 791–795. PubMed doi:10.1016/j.biochi.2009.01.008
Cartwright, I.J., Pockley, A.G., Galloway, J.H., Greaves, M.,
& Preston, F.E. (1985). The effects of dietary omega-3
polyunsaturated fatty acids on erythrocyte membrane
phospholipids, erythrocyte deformability and blood viscosity in healthy volunteers. Atherosclerosis, 55, 267–281.
PubMed doi:10.1016/0021-9150(85)90106-6
Clarke, S.D. (2001). Polyunsaturated fatty acid regulation of
gene transcription: A molecular mechanism to improve
the metabolic syndrome. The Journal of Nutrition, 131,
1129–1132. PubMed
Clarke, S.D., & Jump, D. (1997). Polyunsaturated fatty acids
regulate lipogenic and peroxisomal gene expression
by independent mechanisms. Prostaglandins, Leukotrienes, and Essential Fatty Acids, 57, 65–69. PubMed
doi:10.1016/S0952-3278(97)90494-4
Clavel, S., Farout, L., Briand, M., Briand, Y., & Jouanel, P.
(2002). Effect of endurance training and/or fish oil supplemented diet on cytoplasmic fatty acid binding protein
in rat skeletal muscles and heart. European Journal of
Applied Physiology, 87, 193–201. PubMed doi:10.1007/
s00421-002-0612-6
Coggan, A.R., Kohrt, W.M., Spina, R.J., Bier, D.M., & Holloszy,
J.O. (1990). Endurance training decreases plasma glucose
turnover and oxidation during moderate-intensity exercise
in men. Journal of Applied Physiology (Bethesda, Md.),
68, 990–996. PubMed
Delarue, J., Labarthe, F., & Cohen, R. (2003). Fish-oil
supplementation reduces stimulation of plasma glucose
fluxes during exercise in untrained males. The British
Journal of Nutrition, 90, 777–786. PubMed doi:10.1079/
BJN2003964
Demaison, L., Blet, J., Sergiel, J.P., Gregoire, S., & Argaud, D.
(2000). Effect of dietary polyunsaturated fatty acids on
contractile function of hearts isolated from sedentary and
trained rats. Reproduction, Nutrition, Development, 40,
113–125. PubMed doi:10.1051/rnd:2000124
Dyerberg, J., Bang, H.O., & Hjorne, N. (1975). Fatty acid
composition of the plasma lipids in Greenland Eskimos.
The American Journal of Clinical Nutrition, 28, 958–966.
PubMed
Ernst, E., Saradeth, T., & Achhammer, G. (1991). n-3
fatty acids and acute-phase proteins. European Journal of Clinical Investigation, 21, 77–82. PubMed
doi:10.1111/j.1365-2362.1991.tb01362.x
Filaire, E., Massart, A., Rouveix, M., Portier, H., Rosado, F., &
Durand, D. (2011). Effects of 6 weeks of n-3 fatty acids
and antioxidant mixture on lipid peroxidation at rest and
postexercise. European Journal of Applied Physiology,
111(8), 1829–1839. PubMed doi:10.1007/s00421-0101807-x
Fisher-Wellman, K., & Bloomer, R.J. (2009). Acute exercise
and oxidative stress: A 30 year history. Dynamic Medicine,
8, 1. PubMed doi:10.1186/1476-5918-8-1
Fleischhauer, F.J., Yan, W.D., & Fischell, T.A. (1993). Fish
oil improves endothelium-dependent coronary vasodilation in heart transplant recipients. Journal of the
American College of Cardiology, 21, 982–989. PubMed
doi:10.1016/0735-1097(93)90357-7
Fontani, G., Corradeschi, F., Felici, A., Alfatti, F., Migliorini,
S., & Lodi, L. (2005). Cognitive and physiological effects
of omega-3 polyunsaturated fatty acid supplementation in healthy subjects. European Journal of Clinical
Investigation, 35, 691–699. PubMed doi:10.1111/j.13652362.2005.01570.x
Galea, G., & Davidson, R.J. (1985). Hemorrheology of marathon running. International Journal of Sports Medicine, 6,
136–138. PubMed doi:10.1055/s-2008-1025826
Gans, R.O., Bilo, H.J., Weersink, E.G., Rauwerda, J.A., Fonk,
T., Popp-Snijders, C., & Donker, A.J. (1990). Fish oil
supplementation in patients with stable claudication.
American Journal of Surgery, 160, 490–495. PubMed
doi:10.1016/S0002-9610(05)81012-8
Gingras, A.A., White, P.J., Chouinard, P.Y., Julien, P., Davis,
T.A., Dombrowski, L., . . . Thivierge, M.C. (2007). Longchain omega-3 fatty acids regulate bovine whole-body
protein metabolism by promoting muscle insulin signalling
to the Akt-mTOR-S6K1 pathway and insulin sensitiv-
Omega-3 and Physical Performance 93
ity. The Journal of Physiology, 579, 269–284. PubMed
doi:10.1113/jphysiol.2006.121079
Guezennec, C.Y., Nadaud, J.F., Satabin, P., Leger, F., & Lafargue, P. (1989). Influence of polyunsaturated fatty acid
diet on the hemorrheological response to physical exercise
in hypoxia. International Journal of Sports Medicine, 10,
286–291. PubMed doi:10.1055/s-2007-1024917
Guglielmo, C.G., Haunerland, N.H., Hochachka, P.W., & Williams, T.D. (2002). Seasonal dynamics of flight muscle
fatty acid binding protein and catabolic enzymes in a
migratory shorebird. American Journal of Physiology.
Regulatory, Integrative and Comparative Physiology, 282,
R1405–R1413. PubMed
Guzman, J.F., Esteve, H., Pablos, C., Pablos, A., & Villegas, J.A.
(2011). DHA-rich fish oil improves complex reaction time
in female elite soccer players. Journal of Sports Science
and Medicine, 10, 301–305.
Harris, W.S. (1989). Fish oils and plasma lipid and lipoprotein
metabolism in humans: A critical review. Journal of Lipid
Research, 30, 785–807. PubMed
Helge, J.W., Wu, B.J., Willer, M., Daugaard, J.R., Storlien, L.H.,
& Kiens, B. (2001). Training affects muscle phospholipid
fatty acid composition in humans. Journal of Applied
Physiology (Bethesda, Md.), 90, 670–677. PubMed
Heller, A., Koch, T., Schmeck, J., & van Ackern, K. (1998).
Lipid mediators in inflammatory disorders. Drugs, 55,
487–496. PubMed doi:10.2165/00003495-19985504000001
Herrmann, W., Biermann, J., & Kostner, G.M. (1995). Comparison of effects of N-3 to N-6 fatty acids on serum level of
lipoprotein(a) in patients with coronary artery disease. The
American Journal of Cardiology, 76, 459–462. PubMed
doi:10.1016/S0002-9149(99)80130-1
Hostetler, H.A., Petrescu, A.D., Kier, A.B., & Schroeder, F.
(2005). Peroxisome proliferator-activated receptor alpha
interacts with high affinity and is conformationally responsive to endogenous ligands. The Journal of Biological
Chemistry, 280, 18667–18682. PubMed doi:10.1074/jbc.
M412062200
Hu, F.B., Bronner, L., Willett, W.C., Stampfer, M.J., Rexrode,
K.M., Albert, C.M., . . . Manson, J.E. (2002). Fish and
omega-3 fatty acid intake and risk of coronary heart
disease in women. Journal of the American Medical
Association, 287, 1815–1821. PubMed doi:10.1001/
jama.287.14.1815
Huffman, D.M., Altena, T.S., Mawhinney, T.P., & Thomas, T.R.
(2004). Effect of n-3 fatty acids on free tryptophan and
exercise fatigue. European Journal of Applied Physiology,
92, 584–591. PubMed doi:10.1007/s00421-004-1069-6
Ide, T., Egan, K., Bell-Parikh, L.C., & FitzGerald, G.A. (2003).
Activation of nuclear receptors by prostaglandins. Thrombosis Research, 110, 311–315. PubMed doi:10.1016/
S0049-3848(03)00418-3
Infante, J.P., Kirwan, R.C., & Brenna, J.T. (2001). High levels of
docosahexaenoic acid (22:6n-3)-containing phospholipids
in high-frequency contraction muscles of hummingbirds
and rattlesnakes. Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology, 130,
291–298. PubMed doi:10.1016/S1096-4959(01)00443-2
Jouris, K.B., McDaniel, J.L., & Weiss, E.P. (2011). The effect of
omega-3 fatty acid supplementation on the inflammatory
response to eccentric strength exercise. Journal of Sports
Science and Medicine, 10, 432–438.
Jump, D.B., Clarke, S.D., Thelen, A., & Liimatta, M. (1994).
Coordinate regulation of glycolytic and lipogenic gene
expression by polyunsaturated fatty acids. Journal of Lipid
Research, 35, 1076–1084. PubMed
Kris-Etherton, P.M., Grieger, J.A., & Etherton, T.D. (2009).
Dietary reference intakes for DHA and EPA. Prostaglandins, Leukotrienes, and Essential Fatty Acids, 81, 99–104.
PubMed doi:10.1016/j.plefa.2009.05.011
Kris-Etherton, P.M., Harris, W.S., & Appel, L.J. (2002). Fish
consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation, 106, 2747–2757. PubMed
doi:10.1161/01.CIR.0000038493.65177.94
Leaf, A., Kang, J.X., Xiao, Y.F., & Billman, G.E. (2003).
Clinical prevention of sudden cardiac death by n-3 polyunsaturated fatty acids and mechanism of prevention of
arrhythmias by n-3 fish oils. Circulation, 107, 2646–2652.
PubMed doi:10.1161/01.CIR.0000069566.78305.33
Lee, T.H., Hoover, R.L., Williams, J.D., Sperling, R.I., Ravalese, J., 3rd, Spur, B.W., . . . Austen, K.F. (1985). Effect
of dietary enrichment with eicosapentaenoic and docosahexaenoic acids on in vitro neutrophil and monocyte
leukotriene generation and neutrophil function. The New
England Journal of Medicine, 312, 1217–1224. PubMed
doi:10.1056/NEJM198505093121903
Lemaitre, R.N., King, I.B., Mozaffarian, D., Kuller, L.H., Tracy,
R.P., & Siscovick, D.S. (2003). n-3 polyunsaturated fatty
acids, fatal ischemic heart disease, and nonfatal myocardial infarction in older adults: The Cardiovascular Health
Study. The American Journal of Clinical Nutrition, 77,
319–325. PubMed
Lenn, J., Uhl, T., Mattacola, C., Boissonneault, G., Yates, J.,
Ibrahim, W., & Bruckner, G. (2002). The effects of fish oil
and isoflavones on delayed onset muscle soreness. Medicine and Science in Sports and Exercise, 34, 1605–1613.
PubMed doi:10.1097/00005768-200210000-00012
Lin, Q., Ruuska, S.E., Shaw, N.S., Dong, D., & Noy, N. (1999).
Ligand selectivity of the peroxisome proliferator-activated
receptor alpha. Biochemistry, 38, 185–190. PubMed
doi:10.1021/bi9816094
Lortet, S., & Verger, P. (1995). Alteration of cardiovascular
function in trained rats fed with fish oil. International
Journal of Sports Medicine, 16, 519–521. PubMed
doi:10.1055/s-2007-973047
Maillet, D., & Weber, J.M. (2006). Performance-enhancing role
of dietary fatty acids in a long-distance migrant shorebird:
The semipalmated sandpiper. The Journal of Experimental
Biology, 209, 2686–2695. PubMed doi:10.1242/jeb.02299
Maillet, D., & Weber, J.M. (2007). Relationship between n-3
PUFA content and energy metabolism in the flight muscles
of a migrating shorebird: Evidence for natural doping. The
Journal of Experimental Biology, 210, 413–420. PubMed
doi:10.1242/jeb.02660
Malaguti, M., Baldini, M., Angeloni, C., Biagi, P., & Hrelia, S.
(2008). High-protein-PUFA supplementation, red blood
cell membranes, and plasma antioxidant activity in vol-
94 Mickleborough
leyball athletes. International Journal of Sport Nutrition
and Exercise Metabolism, 18, 301–312. PubMed
McAnulty, S.R., Nieman, D.C., Fox-Rabinovich, M., Duran,
V., McAnulty, L.S., Henson, D.A., . . . Landram, M.J.
(2010). Effect of n-3 fatty acids and antioxidants on
oxidative stress after exercise. Medicine and Science in
Sports and Exercise, 42, 1704–1711. PubMed doi:10.1249/
MSS.0b013e3181d85bd1
Mckenzie, D.J., Higg, D.A., Dosanjh, B.S., Deacon, G., &
Randell, D.J. (1998). Dietary fatty acid composition
influences swimming performance in Atlantic salmon in
seawater. Fish Physiology and Biochemistry, 19, 111–122.
doi:10.1023/A:1007779619087
McLennan, P.L. (2001). Myocardial membrane fatty acids
and the antiarrhythmic actions of dietary fish oil in
animal models. Lipids, 36(Suppl.), S111–S114. PubMed
doi:10.1007/s11745-001-0692-x
Meydani, S.N., Endres, S., Woods, M.M., Goldin, B.R., Soo, C.,
Morrill-Labrode, A., . . . Gorbach, S.L. (1991). Oral (n-3)
fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: Comparison between
young and older women. The Journal of Nutrition, 121,
547–555. PubMed
Mickleborough, T.D. (2008). A nutritional approach to
managing exercise-induced asthma. Exercise and Sport
Sciences Reviews, 36, 135–144. PubMed doi:10.1097/
JES.0b013e31817be827
Mickleborough, T.D., Lindley, M.R., Ionescu, A.A., & Fly,
A.D. (2006). Protective effect of fish oil supplementation
on exercise-induced bronchoconstriction in asthma. Chest,
129, 39–49. PubMed doi:10.1378/chest.129.1.39
Mickleborough, T.D., Murray, R.L., Ionescu, A.A., & Lindley,
M.R. (2003). Fish oil supplementation reduces severity of exercise-induced bronchoconstriction in elite
athletes. American Journal of Respiratory and Critical
Care Medicine, 168, 1181–1189. PubMed doi:10.1164/
rccm.200303-373OC
Mishra, A., Chaudhary, A., & Sethi, S. (2004). Oxidized
omega-3 fatty acids inhibit NF-κB activation via a PPARαdependent pathway. Arteriosclerosis, Thrombosis, and Vascular Biology, 24, 1621–1627. PubMed doi:10.1161/01.
ATV.0000137191.02577.86
Mori, T.A., & Beilin, L.J. (2001). Long-chain omega 3 fatty
acids, blood lipids and cardiovascular risk reduction.
Current Opinion in Lipidology, 12, 11–17. PubMed
doi:10.1097/00041433-200102000-00003
Mori, T.A., Beilin, L.J., Burke, V., Morris, J., & Ritchie, J.
(1997). Interactions between dietary fat, fish, and fish
oils and their effects on platelet function in men at risk of
cardiovascular disease. Arteriosclerosis, Thrombosis, and
Vascular Biology, 17, 279–286. PubMed doi:10.1161/01.
ATV.17.2.279
Mozaffarian, D., Geelen, A., Brouwer, I.A., Geleijnse, J.M.,
Zock, P.L., & Katan, M.B. (2005). Effect of fish oil on heart
rate in humans: A meta-analysis of randomized controlled
trials. Circulation, 112, 1945–1952. PubMed doi:10.1161/
CIRCULATIONAHA.105.556886
Nagahuedi, S., Popesku, J.T., Trudeau, V.L., & Weber, J.M.
(2009). Mimicking the natural doping of migrant sandpip-
ers in sedentary quails: Effects of dietary n-3 fatty acids
on muscle membranes and PPAR expression. The Journal of Experimental Biology, 212, 1106–1114. PubMed
doi:10.1242/jeb.027888
Neschen, S., Morino, K., Dong, J., Wang-Fischer, Y., Cline,
G.W., Romanelli, A.J., . . . Shulman, G.I. (2007). n-3
fatty acids preserve insulin sensitivity in vivo in a peroxisome proliferator-activated receptor-alpha-dependent
manner. Diabetes, 56, 1034–1041. PubMed doi:10.2337/
db06-1206
Nieman, D.C., Henson, D.A., McAnulty, S.R., Jin, F., & Maxwell, K.R. (2009). n-3 polyunsaturated fatty acids do not
alter immune and inflammation measures in endurance
athletes. International Journal of Sport Nutrition and
Exercise Metabolism, 19(5), 536–546. PubMed
Ninio, D.M., Hill, A.M., Howe, P.R., Buckley, J.D., & Saint,
D.A. (2008). Docosahexaenoic acid-rich fish oil improves
heart rate variability and heart rate responses to exercise in
overweight adults. The British Journal of Nutrition, 100,
1097–1103. PubMed doi:10.1017/S0007114508959225
Northoff, H., & Berg, A. (1991). Immunologic mediators as
parameters of the reaction to strenuous exercise. International Journal of Sports Medicine, 12(Suppl. 1), S9–S15.
PubMed doi:10.1055/s-2007-1024743
O’Connor, C.I., Lawrence, L.M., Lawrence, A.C., Janicki,
K.M., Warren, L.K., & Hayes, S. (2004). The effect of
dietary fish oil supplementation on exercising horses.
Journal of Animal Science, 82, 2978–2984. PubMed
Oomen, C.M., Feskens, E.J., Rasanen, L., Fidanza, F., Nissinen, A.M., Menotti, A., . . . Kromhout, D. (2000). Fish
consumption and coronary heart disease mortality in
Finland, Italy, and The Netherlands. American Journal
of Epidemiology, 151, 999–1006. PubMed doi:10.1093/
oxfordjournals.aje.a010144
Oostenbrug, G.S., Mensink, R.P., Hardeman, M.R., De Vries, T.,
Brouns, F., & Hornstra, G. (1997). Exercise performance,
red blood cell deformability, and lipid peroxidation: Effects
of fish oil and vitamin E. Journal of Applied Physiology
(Bethesda, Md.), 83, 746–752. PubMed
Overney, L.S., Blanke, O., & Herzog, M.H. (2008). Enhanced
temporal but not attentional processing in expert tennis
players. PLoS ONE, 3, e2380. PubMed doi:10.1371/
journal.pone.0002380
Paschos, G.K., Magkos, F., Panagiotakos, D.B., Votteas, V., &
Zampelas, A. (2007). Dietary supplementation with flaxseed oil lowers blood pressure in dyslipidaemic patients.
European Journal of Clinical Nutrition, 61, 1201–1206.
PubMed doi:10.1038/sj.ejcn.1602631
Pedersen, H., Petersen, M., Major-Pedersen, A., Jensen, T.,
Nielsen, N.S., Lauridsen, S.T., & Marckmann, P. (2003).
Influence of fish oil supplementation on in vivo and in
vitro oxidation resistance of low-density lipoprotein in
Type 2 diabetes. European Journal of Clinical Nutrition,
57, 713–720. PubMed doi:10.1038/sj.ejcn.1601602
Peoples, G.E., McLennan, P.L., Howe, P.R., & Groeller, H.
(2008). Fish oil reduces heart rate and oxygen consumption during exercise. Journal of Cardiovascular
Pharmacology, 52, 540–547. PubMed doi:10.1097/
FJC.0b013e3181911913
Omega-3 and Physical Performance 95
Phang, M., Sinclair, A.J., Lincz, L.F., & Garg, M.L. (2012).
Gender-specific inhibition of platelet aggregation following omega-3 fatty acid supplementation. Nutrition,
Metabolism, and Cardiovascular Diseases, 22, 109–114.
PubMed doi:10.1016/j.numecd.2010.04.012
Pierce, B.J., McWilliams, S.R., O’Connor, T.P., Place, A.R.,
& Guglielmo, C.G. (2005). Effect of dietary fatty acid
composition on depot fat and exercise performance in
a migrating songbird, the red-eyed vireo. The Journal
of Experimental Biology, 208, 1277–1285. PubMed
doi:10.1242/jeb.01493
Poprzecki, S., Zajac, A., Chalimoniuk, M., Waskiewicz, Z.,
& Langfort, J. (2009). Modification of blood antioxidant
status and lipid profile in response to high-intensity endurance exercise after low doses of omega-3 polyunsaturated
fatty acids supplementation in healthy volunteers. International Journal of Food Sciences and Nutrition, 60(Suppl.
2), 67–79. PubMed doi:10.1080/09637480802406161
Prasad, K. (2009). Flaxseed and cardiovascular health. Journal
of Cardiovascular Pharmacology, 54, 369–377. PubMed
doi:10.1097/FJC.0b013e3181af04e5
Price, E.R. (2010). Dietary lipid composition and avian migratory flight performance: Development of a theoretical
framework for avian fat storage. Comparative Biochemistry and Physiology. Part A, Molecular & Integrative
Physiology, 157, 297–309. PubMed doi:10.1016/j.
cbpa.2010.05.019
Puhakainen, I., Ahola, I., & Yki-Jarvinen, H. (1995). Dietary
supplementation with n-3 fatty acids increases gluconeogenesis from glycerol but not hepatic glucose production
in patients with non-insulin-dependent diabetes mellitus.
The American Journal of Clinical Nutrition, 61, 121–126.
PubMed
Raastad, T., Hostmark, A.T., & Stromme, S.B. (1997). Omega-3
fatty acid supplementation does not improve maximal aerobic power, anaerobic threshold and running performance
in well-trained soccer players. Scandinavian Journal of
Medicine & Science in Sports, 7, 25–31. PubMed
Rissanen, T., Voutilainen, S., Nyyssonen, K., Lakka, T.A., &
Salonen, J.T. (2000). Fish oil-derived fatty acids, docosahexaenoic acid and docosapentaenoic acid, and the risk
of acute coronary events: The Kuopio Ischaemic Heart
Disease Risk Factor study. Circulation, 102, 2677–2679.
PubMed doi:10.1161/01.CIR.102.22.2677
Robinson, J.G., & Stone, N.J. (2006). Antiatherosclerotic
and antithrombotic effects of omega-3 fatty acids. The
American Journal of Cardiology, 98, 39i–49i. PubMed
doi:10.1016/j.amjcard.2005.12.026
Ruf, T., Valencak, T., Tataruch, F., & Arnold, W. (2006). Running speed in mammals increases with muscle n-6 polyunsaturated fatty acid content. PLoS ONE, 1, e65. PubMed
doi:10.1371/journal.pone.0000065
Ryan, A.M., Reynolds, J.V., Healy, L., Byrne, M., Moore,
J., Brannelly, N., . . . Flood, P. (2009). Enteral nutrition
enriched with eicosapentaenoic acid (EPA) preserves
lean body mass following esophageal cancer surgery:
Results of a double-blinded randomized controlled trial.
Annals of Surgery, 249, 355–363. PubMed doi:10.1097/
SLA.0b013e31819a4789
Schoeller, D.A. (1995). Limitations in the assessment of dietary
energy intake by self-report. Metabolism: Clinical and
Experimental, 44, 18–22. PubMed
Sen, C.K. (1995). Oxidants and antioxidants in exercise. Journal of Applied Physiology (Bethesda, Md.), 79, 675–686.
PubMed
Sen, C.K., Atalay, M., Agren, J., Laaksonen, D.E., Roy, S.,
& Hanninen, O. (1997). Fish oil and vitamin E supplementation in oxidative stress at rest and after physical
exercise. Journal of Applied Physiology (Bethesda, Md.),
83, 189–195. PubMed
Shaffer, S.A., Tremblay, Y., Weimerskirch, H., Scott, D.,
Thompson, D.R., Sagar, P.M., . . . Costa, D.P. (2006).
Migratory shearwaters integrate oceanic resources across
the Pacific Ocean in an endless summer. Proceedings of
the National Academy of Sciences of the United States
of America, 103, 12799–12802. PubMed doi:10.1073/
pnas.0603715103
Silvers, K.M., & Scott, K.M. (2002). Fish consumption and
self-reported physical and mental health status. Public
Health Nutrition, 5, 427–431. PubMed doi:10.1079/
PHN2001308
Simchon, S., Jan, K.M., & Chien, S. (1987). Influence of
reduced red cell deformability on regional blood flow.
The American Journal of Physiology, 253, H898–H903.
PubMed
Simopoulos, A.P. (2007). Omega-3 fatty acids and athletics.
Current Sports Medicine Reports, 6, 230–236. PubMed
doi:10.1007/s11932-007-0037-4
Solomon, S.A., Cartwright, I., Pockley, G., Greaves, M.,
Preston, F.E., Ramsay, L.E., & Waller, P.C. (1990). A
placebo-controlled, double-blind study of eicosapentanoic
acid-rich fish oil in patients with stable angina pectoris. Current Medical Research and Opinion, 12, 1–11.
doi:10.1185/03007999009111485
Stebbins, C.L., Hammel, L.E., Marshal, B.J., Spangenberg,
E.E., & Musch, T.I. (2010). Effects of dietary omega-3
polyunsaturated fatty acids on the skeletal-muscle bloodflow response to exercise in rats. International Journal of
Sport Nutrition and Exercise Metabolism, 20, 475–486.
PubMed
Su, W., & Jones, P.J. (1993). Dietary fatty acid composition
influences energy accretion in rats. The Journal of Nutrition, 123, 2109–2114. PubMed
Suarez, R.K., Lighton, J.R., Moyes, C.D., Brown, G.S., Gass,
C.L., & Hochachka, P.W. (1990). Fuel selection in rufous
hummingbirds: Ecological implications of metabolic
biochemistry. Proceedings of the National Academy of
Sciences of the United States of America, 87, 9207–9210.
PubMed doi:10.1073/pnas.87.23.9207
Tartibian, B., Maleki, B.H., & Abbasi, A. (2009). The effects
of ingestion of omega-3 fatty acids on perceived pain and
external symptoms of delayed onset muscle soreness in
untrained men. Clinical Journal of Sport Medicine, 19,
115–119. PubMed doi:10.1097/JSM.0b013e31819b51b3
Terano, T., Hirai, A., Hamazaki, T., Kobayashi, S., Fujita, T.,
Tamura, Y., & Kumagai, A. (1983). Effect of oral administration of highly purified eicosapentaenoic acid on platelet
function, blood viscosity and red cell deformability in
96 Mickleborough
healthy human subjects. Atherosclerosis, 46, 321–331.
PubMed doi:10.1016/0021-9150(83)90181-8
Toft, A.D., Thorn, M., Ostrowski, K., Asp, S., Moller, K.,
Iversen, S., . . . Pedersen, B.K. (2000). N-3 polyunsaturated
fatty acids do not affect cytokine response to strenuous
exercise. Journal of Applied Physiology (Bethesda, Md.),
89, 2401–2406. PubMed
Trimmer, J.K., Schwarz, J.M., Casazza, G.A., Horning, M.A.,
Rodriguez, N., & Brooks, G.A. (2002). Measurement of
gluconeogenesis in exercising men by mass isotopomer
distribution analysis. Journal of Applied Physiology
(Bethesda, Md.), 93, 233–241. PubMed
U.S. Food and Drug Administration. (2004). 21 CFR Part
184 [Docket No.1999P-5332]. Federal Register, 69,
2313–2317.
Ushio, H., Ohishima, T., Koizumi, C., Visuthi, V., Kiron, V.,
& Watanabe, T. (1997). Effect of dietary fatty acids on
Ca2+- ATPase activity of the sarcoplasmic reticulum of
rainbow trout skeletal muscle. Comparative Biochemistry
and Physiology. Part B, Biochemistry & Molecular Biology, 118, 681–691. doi:10.1016/S0305-0491(97)00229-0
Valencak, T.G., Arnold, W., Tataruch, F., & Ruf, T. (2003).
High content of polyunsaturated fatty acids in muscle
phospholipids of a fast runner, the European brown hare
(Lepus europaeus). Journal of Comparative Physiology.
B, Biochemical, Systemic, and Environmental Physiology,
173, 695–702. PubMed doi:10.1007/s00360-003-0382-4
van der Brug, G.E., Peters, H.P., Hardeman, M.R., Schep, G.,
& Mosterd, W.L. (1995). Hemorrheological response
to prolonged exercise—No effects of different kinds of
feedings. International Journal of Sports Medicine, 16,
231–237. PubMed doi:10.1055/s-2007-972997
von Schacky, C., Angerer, P., Kothny, W., Theisen, K., & Mudra,
H. (1999). The effect of dietary omega-3 fatty acids on
coronary atherosclerosis. A randomized, double-blind,
placebo-controlled trial. Annals of Internal Medicine, 130,
554–562. PubMed
Walser, B., Giordano, R.M., & Stebbins, C.L. (2006). Supplementation with omega-3 polyunsaturated fatty acids augments brachial artery dilation and blood flow during forearm contraction. European Journal of Applied Physiology,
97, 347–354. PubMed doi:10.1007/s00421-006-0190-0
Walser, B., & Stebbins, C.L. (2008). Omega-3 fatty acid
supplementation enhances stroke volume and cardiac
output during dynamic exercise. European Journal of
Applied Physiology, 104, 455–461. PubMed doi:10.1007/
s00421-008-0791-x
Warner, J.G., Jr., Ullrich, I.H., Albrink, M.J., & Yeater, R.A.
(1989). Combined effects of aerobic exercise and omega-3
fatty acids in hyperlipidemic persons. Medicine and
Science in Sports and Exercise, 21, 498–505. PubMed
doi:10.1249/00005768-198910000-00003
Yalcin, O., Bor-Kucukatay, M., Senturk, U.K., & Baskurt, O.K.
(2000). Effects of swimming exercise on red blood cell
rheology in trained and untrained rats. Journal of Applied
Physiology (Bethesda, Md.), 88, 2074–2080. PubMed
Yamori, Y., Nara, Y., Iritani, N., Workman, R.J., & Inagami,
T. (1985). Comparison of serum phospholipid fatty
acids among fishing and farming Japanese populations
and American inlanders. Journal of Nutritional Science
and Vitaminology, 31, 417–422. PubMed doi:10.3177/
jnsv.31.417
Zhao, G., Etherton, T.D., Martin, K.R., West, S.G., Gillies, P.J.,
& Kris-Etherton, P.M. (2004). Dietary alpha-linolenic acid
reduces inflammatory and lipid cardiovascular risk factors
in hypercholesterolemic men and women. The Journal of
Nutrition, 134, 2991–2997. PubMed