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J.J.F.P. Luiken, D. Miskovic, Y. Arumugam, J.F.C. Glatz and A. Bonen

While it has long been assumed that long chain fatty acids (LCFA) can freely diffuse across the plasma membrane, recent work has shown that LCFA uptake also involves a protein-mediated mechanism. Three putative LCFA transporters have been identified (FABPpm, FATP, and FAT/CD36), and all are expressed in rodent and human muscles. In a new model system (giant vesicles), we have demonstrated that (a) LCFA transport rates are scaled with the oxidative capacity of heart and muscle, (b) only FABPpm and FAT/CD36, but not FATP1, correlate with vesicular LCFA transport, and (c) LCFA transport can be increased by increasing (1) the FAT/CD36 protein of muscle (chronic adaptation) or (2) via the translocation of FAT/CD36 from an intracellular pool to the plasma membrane during muscle contraction (acute adaptation).

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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.

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Paraskevi Detopoulou and Vasilios Papamikos

Omega-3 fatty acids exert a plethora of physiological actions including triglycerides lowering, reduction of inflammatory indices, immunomodulation, anti- thrombotic effects and possibly promotion of exercise performance. Their use is widespread and for commonly ingested doses their side- effects are minimal. We report a case of a 60y amateur athlete who consumed about 20 g omega-3 fatty acids daily from supplements and natural sources for a year. After the intake of cortisone and antibiotics he presented duodenum ulcer and bleeding although he had no previous history of gastrointestinal problems. Although several animal data support gastro-protective effects of omega-3 fatty acids in the present case they were not able to prevent ulcer generation. The present observation may be explained by (i) the high dose of omega-3 fatty acids and their effect on bleeding, (ii) the fact that cortisone increases their oxidation and may render them proinflammatory, (iii) other antithrombotic microconstituents included in the consumed cod-oil and/or the diet of the subject and (iv) the differences in the coagulation and fibrinolytic systems of well- trained subjects. Further studies are needed to substantiate any possible interaction of cortisone and omega-3 fatty acids in wide ranges of intake.

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Patrick B. Wilson and Leilani A. Madrigal

Omega-3 polyunsaturated fatty acids (PUFAs) have important physiological functions and may offer select benefits for athletic performance and recovery. The purpose of this investigation was to assess dietary and whole blood omega-3 PUFAs among collegiate athletes. In addition, a brief questionnaire was evaluated as a valid tool for quantifying omega-3 PUFA intake. Fifty-eight athletes (9 males, 49 females) completed a 21-item questionnaire developed to assess omega-3 PUFA intake and provided dried whole blood samples to quantify α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and the HS-Omega-3 Index. Geometric means (95% confidence intervals) for the HS-Omega-3 Index were 4.79% (4.37–5.25%) and 4.75% (4.50–5.01%) for males and females, respectively. Median dietary intakes of ALA, EPA, and DHA were all below 100 mg. Among females, several dietary omega-3 PUFA variables were positively associated with whole blood EPA, with total EPA (rho = 0.67, p < .001) and total DHA (rho = 0.69, p < .001) intakes showing the strongest correlations. Whole blood DHA among females showed positive associations with dietary intakes, with total EPA (rho = 0.62, p < .001) and total DHA (rho = 0.64, p < .001) intakes demonstrating the strongest correlations. The HS-Omega-3 Index in females was positively correlated with all dietary variables except ALA. Among males, the only significant correlation was between food and whole blood EPA (rho = 0.83, p < .01). Collegiate athletes had relatively low intakes of omega-3 PUFAs. A 21-item questionnaire may be useful for screening female athletes for poor omega-3 PUFA status.

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Edith Filaire, Alain Massart, Hugues Portier, Matthieu Rouveix, Fatima Rosado, Anne S. Bage, Mylène Gobert and Denys Durand

The aim of this investigation was to assess the effects of 6 wk of eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) supplementation on resting and exercise-induced lipid peroxidation and antioxidant status in judoists. Subjects were randomly assigned to receive a placebo or a capsule of polyunsaturated fatty acids (PUFAs; 600 mg EPA and 400 mg DHA). Blood samples were collected in preexercise and postexercise conditions (judo-training session), both before and after the supplementation period. The following parameters were analyzed: α-tocopherol, retinol, lag phase, maximum rate of oxidation (Rmax) during the propagating chain reaction, maximum amount of conjugated dienes (CDmax) accumulated after the propagation phase, nitric oxide (NO) and malondyaldehide (MDA) concentrations, salivary glutathione peroxidase activity, and the lipid profile. Dietary data were collected using a 7-day dietary record. A significant interaction effect between supplementation and time (p < .01) on triglycerides was noted, with values significantly lower in the n-3 long-chain-PUFA (LCPUFA) group after supplementation than in the placebo group. Significant interaction effects between supplementation and time on resting MDA concentrations and Rmax were found (p = .03 and p = .04, respectively), with elevated values in the n-3 LCPUFA group after supplementation and no change in the placebo group’s levels. The authors observed a significantly greater NO and oxidative-stress increase with exercise (MDA, Rmax, CDmax, and NO) in the n-3 LCPUFA group than with placebo. No main or interaction effects were found for retinol and α-tocopherol. These results indicate that supplementation with n-3 LCPUFAs significantly increased oxidative stress at rest and after a judo-training session.

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David C. Nieman, Dru A. Henson, Steven R. McAnulty, Fuxia Jin and Kendra R. Maxwell

The purpose of this study was to test the influence of 2.4 g/d fish oil n-3 polyunsaturated fatty acids (n-3 PUFA) over 6 wk on exercise performance, inflammation, and immune measures in 23 trained cyclists before and after a 3-d period of intense exercise. Participants were randomized to n-3 PUFA (n = 11; 2,000 mg eicosapentaenoic acid [EPA], 400 mg docosahexaenoic acid [DHA]) or placebo (n = 12) groups. They ingested supplements under double-blind methods for 6 wk before and during a 3-d period in which they cycled for 3 hr/d at ~57% Wmax with 10-km time trials inserted during the final 15 min of each 3-hr bout. Blood and saliva samples were collected before and after the 6-wk supplementation period, immediately after the 3-hr exercise bout on the third day, and 14 hr postexercise and analyzed for various immune-function and inflammation parameters. Supplementation with n-3 PUFA resulted in a significant increase in plasma EPA and DHA but had no effect on 10-km time-trial performance; preexercise outcome measures; exercise-induced increases in plasma cytokines, myeloperoxidase, blood total leukocytes, serum C-reactive protein, and creatine kinase; or the decrease in the salivary IgA:protein ratio. In conclusion, 6 wk supplementation with a large daily dose of n-3 PUFAs increased plasma EPA and DHA but had no effect on exercise performance or in countering measures of inflammation and immunity before or after a 3-d period of 9 hr of heavy exertion.

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Hermann Zbinden-Foncea, Luc J. C. van Loon, Jean-Marc Raymackers, Marc Francaux and Louise Deldicque

Mitogen-activated protein kinase (MAPK) pathways are activated in skeletal muscle during endurance exercise, but the upstream molecular events are incompletely resolved. As an increase in plasma nonesterified fatty acids (NEFA) is a common feature of long-lasting exercise, the authors tested the hypothesis that NEFA contribute to the activation of MAPK during endurance exercise. Acipimox was used before and during endurance exercise to prevent the elevation of plasma NEFA levels in healthy subjects and patients with diabetes. In 2 separate studies, healthy subjects cycled for 2 hr and patients with diabetes for 1 hr at 50% Wmax. In control conditions, plasma NEFA concentrations increased from 0.35 to 0.90 mM during exercise in healthy subjects and from 0.55 to 0.70 mM in patients with diabetes (p < .05). Phosphorylation states of extracellularly regulated kinase 1 and 2 (ERK1/2), p38, and c-Jun NH2-terminal kinases (JNK) were significantly increased after exercise in the vastus lateralis in both groups. Acipimox blocked the increase in plasma NEFA concentrations and almost completely repressed any rise in ERK1/2 and p38 but not in JNK. In conclusion, the data support a role for plasma NEFA in the activation of p38 and ERK1/2 in skeletal-muscle tissue of healthy and diabetic subjects during endurance exercise. Further investigation will be required to determine the molecular link between NEFA and MAPK activation during exercise in human skeletal muscle.

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Mahmoud S. El-Sayed, Angelheart J.M. Rattu, Xia Lin and Thomas Reilly

We examined the effects of active warm-down (AWD) and carbohydrate ingestion on plasma levels of free fatty acids (FFAs) and glucose changes into recovery following prolonged submaximal exercise. Subjects in Group 1 cycled at 70% of maximal oxygen uptake (VO2max); carbohydrate (CHO) or placebo (PLA) was ingested 15 min before and 45 min during exercise. In the AWD experiment, exercise was followed immediately by an AWD and subjects were given a placebo solution. Group 2 subjects consumed CHO or PLA at 75 min during and after exercise at 70% VO2max. ANOVA revealed a significant decrease in blood glucose levels only in Group 1, with a concomitant increase in FFA concentrations during exercise in both groups. Carbohydrate ingestion in Groups 1 and 2 significantly decreased the normal response of FFAs during exercise and markedly reduced the normal elevation of FFAs in recovery. AWD following submaximal exercise had no effect on plasma FFA elevations in recovery. These results suggest that carbohydrate ingestion, but not active warm-down, attenuates FFA elevations in recovery.

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Charles L. Stebbins, Lauren E. Hammel, Benjamin J. Marshal, Espen E. Spangenberg and Timothy I. Musch

The polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) affect vascular relaxation and involve factors (e.g., nitric oxide) that contribute to exercise-induced increases in skeletal-muscle blood flow (Q). The authors investigated whether DHA and EPA supplementation augments skeletal-muscle Q and vascular conductance (VC) and attenuates renal and splanchnic Q and VC in exercising rats. Rats were fed a diet of 5% lipids by weight, of which 20% was DHA and 30% EPA (PUFA group, n = 9), or 5% safflower oil (SO group, n = 8) for 6 wk. Heart rate (HR), blood pressure (MAP), and hind-limb, renal, and splanchnic Q were measured at rest and during moderate treadmill running. MAP, HR, and renal and splanchnic Q and VC were similar between the 2 groups at rest and during exercise. In the PUFA group, Q (158 ± 27 vs. 128 ± 28 ml · min−1 · 100 g−1) and VC (1.16 ± 0.21 vs. 0.92 ± 0.23 ml · min−1 · 100 g−1 · mm Hg−1) were greater in the exercising hind-limb muscle. Q and VC were also higher in 8 of 28 and 11 of 28 muscles and muscle parts, respectively. These increases were positively correlated to the percent sum of Types I and IIa fibers. Results suggest that DHA+EPA (a) enhances Q and VC in active skeletal muscle (especially Type I and IIa fibers) and that the increase in Q is due to an increase in cardiac output secondary to increases in VC and (b) has no apparent influence on vasoconstriction in renal and splanchnic tissue.

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Steven R. McAnulty, David C. Nieman, Lisa S. McAnulty, Worley S. Lynch, Fuxia Jin and Dru A. Henson

Consumption of plant flavonoids, antioxidants, and n-3 fatty acids is proposed to have many potential health benefits derived primarily through antioxidant and anti-inflammatory activities. This study examined the effects of 1,000 mg quercetin + 1,000 mg vitamin C (QC); 1,000 mg quercetin, 1,000 mg vitamin C, 400 mg isoquercetin, 30 mg epigallocatechin gallate, and 400 mg n-3 fatty acids (QFO); or placebo (P), taken each day for 2 wk before and during 3 d of cycling at 57% Wmax for 3 hr, on plasma antioxidant capacity (ferricreducing ability of plasma [FRAP], oxygen-radical absorbance capacity [ORAC]), plasma oxidative stress (F2-isoprostanes), and plasma quercetin and vitamin C levels. Thirty-nine athletes were recruited and randomized to QC, QFO, or P. Blood was collected at baseline, after 2 wk supplementation, immediately postexercise, and 14 hr postexercise. Statistical design used a 3 (groups) × 4 (times) repeated-measures ANOVA with post hoc analyses. Plasma quercetin was significantly elevated in QC and QFO compared with P. Plasma F2-isoprostanes, FRAP, and vitamin C were significantly elevated and ORAC significantly decreased immediately postexercise, but no difference was noted in the overall pattern of change. Post hoc analyses revealed that the QC and QFO groups did not exhibit a significant increase in F2-isoprostanes from baseline to immediately postexercise compared with P. This study indicates that combining flavonoids and antioxidants with n-3 fatty acids is effective in reducing the immediate postexercise increase in F2-isoprostanes. Moreover, this effect occurs independently of changes in plasma antioxidant capacity.