Eicosapentaenoic Acid and Docosahexanoic Acid in Exercise Performance

C H A P T E R

62 Eicosapentaenoic Acid and Docosahexanoic Acid in Exercise Performance Eisuke Ochi Faculty of Bioscience and Applied Chemistry, Hosei University, Tokyo, Japan

INTRODUCTION Nutritional intake helps in improving and maintaining performance in competitive sports. However, there remain unclear points regarding the nutritional effects and related mechanisms including optimal dose, duration, and timing. Omega-3 fatty acids belong to the n-3 polyunsaturated fatty acid family. Omega-3 fatty acids contain large amounts of eicosapentaenoic acid (EPA; 20:5 n-3) and docosahexaenoic acid (DHA; 22:6 n-3), which are mainly contained in fish oil. Omega-3 fatty acids first garnered attention when it was found that the heart disease rate was markedly low in the Greenland Eskimos, who consumed large amounts of these fatty acids [1,2]. Since then, many studies have been published, making it widely known that omega-3 fatty acids are effective for improving cardiac function and blood flow, lowering blood pressure, and improving depression and cognitive function [3–10]. In terms of involvement with exercise performance, EPA and DHA are known in particular to improve fatigue recovery and endurance performance, as well as maintain immune function [5,11,12]. In addition, exhaustive or unaccustomed exercise causes muscle fatigue and delayed onset muscle soreness (DOMS), resulting in decreased exercise performance [13–15]. At the same time, oxidative stress and inflammatory responses have also been occur [16,17]. Previous reports have investigated these topics as EPA and DHA are anticipated to be effective against such reactions [18–21]. Although there is no consensus among researchers regarding some of the points, it is considered possible that EPA and DHA can improve exercise performance. This review focuses on the effects of EPA and DHA on exercise performance as evaluated by human and animal experiments. Specifically, I summarize these effects on (1) endurance and cardiovascular function, (2) muscle and nerve damage, and (3) muscle mass and strength based on past studies.

EPA AND DHA FOR ENDURANCE AND CARDIOVASCULAR FUNCTION Endurance Function EPA and DHA supplementation has been confirmed in both humans and animals to alter the composition of red blood cells and the cell membrane of the myocardium and skeletal muscles [35–37]. It has been demonstrated that 12-week intake of omega-3 fatty acids (EPA: 2.4 g/day; DHA: 1.2 g/day) increased red blood cell deformability [35]. Because increased red blood cell deformability raises oxygen supply through peripheral circulation to the skeletal muscles, it is thought to improve endurance performance [20] (Table 62.1). Raastad et al. [22] investigated male soccer players who belonged to the soccer league in Norway and found that the intake of 1.6 g/day of EPA and 1.0 g/day of DHA for 10 weeks resulted in no change to maximum oxygen uptake (VO2max). Also it has been shown that male cyclists who trained on a daily basis found that the intake of 0.8 g/day of EPA and 2.4 g/day of DHA for 8 weeks did not increase VO2max [23]. Meanwhile a study of elite male cyclists (VO2max was 69.8 ± 4.9 mL/kg per min, and the mean individual monthly training volume was 655 ± 53 km) found that the

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TABLE 62.1  Summary of the Effects of EPA/DHA Supplementation on Endurance and Cardiovascular Function References

Population (Age)

Dose (Per Day)

Duration

Exercise

Outcome

Raastad et al. [22]

28 well-trained male soccer players (18–35 y)

1.6 g of EPA and 1.0 g of DHA

10 weeks

Two trials on the treadmill to determine VO2max, anaerobic threshold, and running performance

VO2max − Anaerobic threshold − Running performance −

Peoples et al. [23]

16 trained cyclists (23.2 ± 1.2 y)

0.80 g of EPA and 2.4 g of DHA

8 weeks

Peak O2 consumption tests and sustained submaximal exercise test at 55% peak workload on an electronically braked cycle ergometer

HR + VO2max − Rate pressure product +

Żebrowska et al. [12]

13 elite male cyclists (23.1 ± 5.4 y)

0.66 g of EPA and 0.44 g of DHA

3 weeks

The regular cycling training and the mean individual monthly training volume were 655 ± 53 km

HR − Systolic blood pressure + Diastolic blood pressure − VO2max + VO2 +

Kawabata et al. [24]

20 recreational males (fish oil group: 23 ± 1 y, placebo group: 23 ± 0 y)

0.914 g of EPA and 0.399 g of DHA

8 weeks

30-min cycling exercise at 2-mM workload, followed by 30 min of cycling exercise at 3-mM workload, with a 10-min rest between the two sessions

HR − VO2max − VO2 + Ventilatory volume −

Clark et al. [25]

14 elderly males and females (25.0 ± 0.5 y), 15 elderly males and females (63.5 ± 1.7 y)

0.90 g of EPA and DHA

12 weeks

15-s bouts of isometric handgrip at 10%, 30%, 50%, and 70% maximal voluntary contraction

Beat-to-beat systolic blood pressure − Arterial blood pressure + HR −

Delodder et al. [26]

4 healthy males and 4 Intravenous healthy females (23–24.5 y) administration, 0.12 g/kg of EPA and 0.11 g/kg of DHA; oral supplementation, 0.12 g of EPA and 0.333 g of DHA

Intravenous administration, 3 h; oral supplementation, 3 days

4 min at 50 W, the workload was increased by 25-W steps every 2 min. The test could be stopped voluntarily or when the pedaling frequency could not be sustained or reached 20 on the Borg scale

HR + Maximal power output + Peak blood lactate +

Ninio et al. [27]

46 sedentary, overweight 0.36 g of EPA and (BMI > 25 kg/m2) adults 1.56 g of DHA with additional risk factors for CVD (25–65 y)

12 weeks

20-min moderate walking speed on an electronic treadmill

HR variability + HR +

Logan and Spriet [28]

24 healthy elderly females (66 ± 1 y)

2.0 g of EPA and 1.0 g of DHA

12 weeks

30-min low intensity cycling exercise

Resting metabolic rate + Energy expenditure + Rate of fat oxidation + Triglyceride + Timed Up and Go Test + Grip strength − VO2 + HR +

Buckley et al. [4]

29 professional Australian football league players (fish oil group: 21.7 ± 1.0 y, placebo group: 23.2 ± 1.1 y)

0.36 g of EPA and 1.56 g of DHA

5 weeks

A treadmill run to exhaustion

HR + Time to exhaustion −

Walser and Stebbins [29]

21 healthy males and healthy females (37 ± 3 y)

3.0 g of EPA and 2.0 g of DHA

6 weeks

20-min pedaling at workload was increased by 25 W every 2 min on a recumbent bicycle ergometer

Stroke volume + Cardiac output + Systemic vascular resistance +

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TABLE 62.1  Summary of the Effects of EPA/DHA Supplementation on Endurance and Cardiovascular Function—cont’d References

Population (Age)

Dose (Per Day)

Duration

Exercise

Outcome

Macartney et al. [11]

39 healthy males (18–40 y)

0.14 g of EPA and 0.56 g of DHA

8 weeks

10-min submaximal cycling at 125 W, 6 × 30 s of Wingate cycling sprints/150 s of recovery, and 5-min work capacity trial

Mean exercise HR + Improved HR recovery + Peak HR −

O’Keefe et al. [30]

18 white males with a history of myocardial infarction and ejection fractions (67.8 ± 6.5 y)

0.225 g of EPA and 0.585 g of DHA

4 months

Subjects were in the supine position for 8 min, followed by 8 min of standing and 60 min of sitting at rest

HR + Stroke volume + HR variability + HR recovery +

Da Boit et al. [31]

37 healthy males and females, (25.8 ± 5.3 y)

0.24 g of EPA and 0.12 g of DHA

6 weeks

Cycling time trial to fixed (70% of Wmax, 80 rpm)

HR − VO2 −

Gray et al. [32]

16 healthy males (24.0 ± 23.8 y)

1.3 g of EPA and 0.30 g of DHA

6 weeks

1-h cycling (70% VO2max)

HR − VO2 −

Rontoyanni et al. [33]

22 healthy males (23.0 ± 3.6 y)

EPA group: 4.7 g of EPA and 1.1 g of DHA DHA group: 0.7 g of EPA and 4.7 g of DHA

1 time

12-min multistage exercise stress test of moderate intensity on a programmable electrically braked cycle ergometer

Blood pressure − Cardiac output − Systemic vascular resistance + Stroke volume − HR −

Walser et al. [34]

13 healthy males and females (26–57 y)

3.0 g of EPA and 2.0 g of DHA

6 weeks

Two 90-s periods of handgrip Brachial artery exercise at 30% MVC and a rate diameter + of one contraction per second Blood pressure − HR −

CVD, cardiovascular disease; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; HR, heart rate; MVC, maximal voluntary isometric contraction.

intake of 0.66 g/day of EPA and 0.44 g/day of DHA for 3 weeks resulted in a significant increase in VO2max [12]. In another study, 20 young untrained males were divided into a group of 10 subjects who ingested 0.914 g/day of EPA and 0.399 g/day of DHA for 8 weeks and a group of 10 subjects who ingested a placebo containing medium-chain triglycerides, and VO2max was measured before and after supplement intake [24]. The results indicated that no difference in VO2max was found between the two groups [24]. The effect of EPA and DHA supplementation on improving VO2max is unclear based on the results to date. Otherwise it has been demonstrated the effect of EPA and DHA on exercise economy during exercise. Exercise economy has been demonstrated to strongly correlate with endurance performance [38]. In the aforementioned study by Kawabata et al. [24], they tested oxygen uptake under submaximal exercise with the same lactic acid conditions and revealed that the group that ingested EPA and DHA had less oxygen uptake during exercise than the placebo group [24]. Moreover it has been demonstrated that rating of perceived exertion during exercise decreased as a result of EPA and DHA supplementation [24]. Thus it appears that the supplementation of EPA and DHA improves exercise economy and can make it easier to continue the exercise. In fact Huffman et al. [39] conducted a study in which subjects ingested 0.3 g/day of EPA and 0.2 g/day of DHA for 4 weeks before running exercise at 60% VO2max. As a result they found that the EPA and DHA group had a longer exercise time until exhaustion compared with the placebo group. Thus it appears that although the intake of EPA and DHA may have a limited effect on VO2max, it is effective in improving exercise economy and perceived exertion during submaximal exercise. The effects on endurance performance in peripheral muscle have been investigated with animal experiments. It showed that three bouts of electrical muscle contractions (10 min) for the ankle plantar flexor muscles with 30-min intervals caused an inhibition in muscle force deficit with the 8-week ingestion of EPA and DHA compared with the saturated fatty acid or omega-6 fatty acid [40]. Furthermore, the recovery rate for muscle force between one bout and three bouts was significantly higher in the EPA and DHA group [40]. In addition, oxygen consumption during exercise was smaller in EPA and DHA group than the other groups [40]. These results suggest that one of the mechanisms for endurance performance improvement with EPA and DHA is caused by reduction of the oxygen cost for muscle contraction (oxygen availability). However, no investigation has examined the effects of EPA and DHA ingestion on local muscle endurance in humans. Therefore we verified the effects on muscle endurance performance of elbow flexors after 0.6 g/day of EPA and 0.26 g/day of DHA for 8 weeks. Our results showed that the decrease

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in work output during muscle contractions was more inhibited in the EPA and DHA group than the placebo group (unpublished data). Accordingly EPA and DHA supplementation may improve endurance performance in peripheral muscles. Continued investigations of these effects on endurance performance in human are required.

Cardiovascular Function It has been clarified that the intake of EPA and DHA improves cardiovascular function [6,28]. In particular, previous reports have found that EPA and DHA supplementation affects heart rate (HR) [25–27]. Logan and Spriet [28] reported that intake of 2.0 g/day of EPA and 1.0 g/day of DHA for 12 weeks showed a decrease in HR at rest in elderly individuals (60–74 years). Similarly it showed that Australian football players with 0.36 g/day of EPA and 1.56 g/day of DHA for 5 weeks resulted in decreased HR at rest and during submaximal exercise [4]. Walser and Stebbins [29] found that trained subjects with 3.0 g/day of EPA and 2.0 g/day of DHA for 6 weeks increased stroke volume and cardiac output during 20-min cycling (starting from 25 W and increasing by 25 W every 2 min). Therefore it seems that increased stroke volume and cardiac output have a role in decreasing HR, resulting from EPA and DHA intake. It has been shown that bicycle pedaling exercise with 0.14 g/day of EPA and 0.56 g/day of DHA for 8 weeks improved the recovery of HR immediately after exercise [11]. Similarly O’Keefe et al. [30] found that patients with myocardial infarctions and depressed ejection fractions improved postexercise HR recovery with 0.225 g/day of EPA and 0.585 g/day of DHA daily for 4 months. On the contrary it has also been reported that the ingestion of EPA and DHA showed no change in HR during at rest or submaximal exercise [31–33]. Thus although improvement of cardiac function can be assumed by the ingestion of EPA and DHA, it should be necessary to investigate the factors such as dose, period, and exercise load in more detail in the future (Table 62.1). In terms of the effects of EPA and DHA ingestion on vascular function, the ingestion of 3.0 g/day of EPA and 2.0 g/ day of DHA for 6 weeks increased blood vessel diameter and vascular blood flow by gripping exercise at 30% maximal voluntary isometric contraction [34]. It has also been reported that hypertensive patients (systolic phase blood pressure: 138.7 ± 5.0 mmHg) ingested 0.9 g/day of EPA and 1.5 g/day of DHA for 24 months, thereby their systolic phase blood pressure decreased by 2.6 ± 2.5 mmHg [41]. In addition, a meta-analysis verifying the effects of EPA and DHA intake on vascular endothelium function according to flow mediated dilation (FMD) testing revealed improvement of 1.4% [42]. Thus it can be concluded that the supplementation of EPA and DHA has positive effect on vascular function at rest and during submaximal exercise.

EPA AND DHA FOR MUSCLE AND NERVE DAMAGE Eccentric contractions (ECCs) cause decreased muscle strength, DOMS, limited range of motion (ROM), and muscle swelling [14,16,43]. While DOMS peaks 1–3 days after exercise [14,16,21], it is uncomfortable and a negative effect for continuing the exercise and training. Because it can also cause decreased muscle strength, reduced flexibility, and lowered exercise performance, the prevention and alleviation of muscle damage after ECCs is an important problem. Muscle damage caused by ECCs is thought to be caused by microdamage of muscle fibers and subsequent inflammation and oxidative stress [44–46]. Because the researchers have studied the effects of omega-3 fatty acids on these phenomena [19,21,47–54], I summarize the findings of previous studies for each topic in the following section.

Muscle Strength Deficit There are few reports on the supplementation of EPA and DHA that is effective against decreased muscle strength caused by ECCs. Houghton and Onambele [55] evaluated a resistance exercise for the lower limbs after 0.36 g/day of ingestion of EPA over 3 weeks and demonstrated no significant differences in muscle strength reduction between the EPA and placebo. Also DiLorenzo et al. [56] found that the subjects with only 2.0 g/day of DHA for 4 weeks did not differ in muscle strength after 60 ECCs in elbow flexors, and Lenn et al. [57] reported that ingestion of 0.287 g/day of EPA and 0.194 g/day of DHA for 30 days did not reduce the decrease in muscle strength after 50 ECCs. Based on the results of these studies we applied 30 ECCs in elbow flexors after the long-term intake of both 0.6 g/day of EPA and 0.26 g/day of DHA for 8 weeks. From the results, we found that ingestion of EPA and DHA caused an inhibition in torque deficit (17%; Fig. 62.1A) [21]. Taken together the effect of EPA and DHA

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EPA and DHA for Muscle and Nerve Damage

(A)

(B)

(C)

(D)

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FIGURE 62.1  Changes (mean ± SD) in maximal voluntary isometric contraction (MVC) torque (A), muscle soreness (B), range of motion (ROM) (C), and interleukin-6 (D) before (pre), immediately after (post), and 1, 2, 3, and 5 days after eccentric contractions in EPA group and placebo. *P < .05, a significant difference between the groups; †P < .05, a significant difference from preexercise value in the EPA group; #P < .05, a significant difference from preexercise value in the placebo group. DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; SD, standard deviation. Data are from Tsuchiya Y, Yanagimoto K, Nakazato K, Hayamizu K, Ochi E. Eicosapentaenoic and docosahexaenoic acids-rich fish oil supplementation attenuates strength loss and limited joint range of motion after eccentric contractions: a randomized, double-blind, placebo-controlled, parallel-group trial. Eur J Appl Physiol 2016;116:1179–1188.

supplementation on strength loss after ECCs is controversial. However, because it was reported that the period of 30- to 60-day ingestion is needed to result in uptake by the human myocardial membrane [59], to achieve the inhibition of muscle strength deficit by EPA and DHA intake, it seems to be important to ingest more than an 8-week period (Table 62.2).

Delayed Onset Muscle Soreness Many studies have reported the effects of EPA and DHA intake on DOMS [21,49,50,54]. Taribian et al. reported that the supplementation of 0.324 g/day of EPA and 0.216 g/day of DHA daily for 30 days inhibited DOMS after 40-min bench stepping [52]. Jouris et al. [48] reported the effect of 2.0 g/day of EPA and 1.0 g/day of DHA for 2 weeks on DOMS after ECCs at 120% 1-repetition maximum (RM) until exhaustion using dumbbells. They observed that the prevention of DOMS has been occurred in the EPA and DHA group. The finding is consistent with our data (0.6 g/day of EPA and 0.26 g/day of DHA for 8 weeks; Fig. 62.1B) [21]. Meanwhile it has been shown that the ingestion of a single DHA or EPA supplement had no effect on DOMS [51,56]. Although the dose and period are different from the previous studies, I suggest that the ingestion of both EPA and DHA may be important in reducing DOMS and has a synergistic effect on attenuation of DOMS, especially at the ratio of approximately 2:1. Otherwise DOMS after ECCs for knee flexors did not change with or without EPA and DHA supplement (1.3 g/day of EPA and 0.3 g/day of DHA for 6 weeks) [58]. Thus these findings suggest that EPA and DHA supplementation has a certain effect to inhibit DOMS by ECCs, but it may differ depending on the dose of EPA and DHA and the exercise site (Table 62.3).

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TABLE 62.2  Summary of the Effects of EPA/DHA Supplementation on Muscle Strength Deficit References

Population (Age)

Dose (Per Day)

Houghton and Onambele [55]

17 healthy females 0.36 g of EPA (20.4 ± 2.3 y)

Duration Exercise

Outcome

3 weeks

Resistance exercise (leg flexions, leg extensions, Ineffective straight leg deadlifts, walking lunges; three sets of 10 repetitions at 70% 1RM)

DiLorenzo et al. [56] 41 healthy, untrained males (21.8 ± 2.7 y)

2.0 g of DHA

4 weeks

Elbow flexor eccentric contractions (six sets of 10 repetitions at 140% 1RM using dumbbells)

Ineffective

Lenn et al. [57]

13 males (22.7 ± 3.9 y) and 9 females (24.5 ± 5.5 y)

0.287 g of EPA and 0.194 g of DHA

30 days

Elbow flexor eccentric contractions (50 maximal effort at 90 degrees/s using the Kin-Com dynamometer)

Ineffective

Gray et al. [58]

20 healthy, untrained males (23.0 ± 2.3 y)

1.30 g EPA and 0.30 g DHA

6 weeks

Knee extensor eccentric contractions (20 sets of 10 repetitions at 0.52 rad/s using the Biodex isokinetic dynamometer)

Ineffective

Tsuchiya et al. [21]

24 healthy, untrained males (19.5 ± 0.8 y)

0.60 g of EPA and 0.26 g of DHA

8 weeks

Elbow flexor eccentric contractions (six sets of maximal five repetitions at 30 degrees/s using the Biodex isokinetic dynamometer)

Effective

Ochi et al. [50]

21 healthy, untrained males (21.0 ± 0.8 y)

0.60 g of EPA and 0.26 g of DHA

8 weeks

Elbow flexor eccentric contractions (six sets of 10 Effective repetitions at 40% 1RM, 30 degrees/s using dumbbells)

DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; RM, repetition maximum.

Range of Motion There have been few studies on the effects of EPA and DHA on the decrease in ROM after ECCs [21,49,50,52,57]. Taribian et al. reported that EPA and DHA attenuated ROM reduction after 40-min bench stepping [52]. Our study also found that 0.6 g/day of EPA and 0.26 g/day of DHA for 8 weeks caused the decrease in ROM reduction (Fig. 62.1C) [21,50]. In contrast, two other studies reported that there was no effect on ROM reduction after ECCs of elbow flexors [49,57]. Thus no fixed consensus has been reached regarding the effects of EPA and DHA intake on ROM reduction. Because decreased flexibility may contribute to reduced exercise performance and increase the risk of injuries, I hope that further studies will become available in the future on the effects of EPA and DHA ingestion on flexibility, including muscle stiffness (Table 62.4).

Swelling (Circumference and Cross-sectional Area) Excessive muscular exercise including ECCs causes muscle swelling [16]. Regarding the relationship between EPA and DHA ingestion and muscle swelling, Taribian et al. [52] only found that the EPA and DHA inhibited the increases in thigh circumference after bench stepping. Other studies did not find the difference between treatment and placebo group in thigh or upper arm circumference [21,48,54]. It appears that these results may have been caused by the variation and precision in tape measurement. Therefore we evaluated the cross-sectional area (CSA) of elbow flexors using ultrasound [50]. Our results indicated that although there was no significant difference, EPA and DHA did show a tendency of inhibiting effect. More precise CSA evaluation using magnetic resonance imaging needs to be conducted [14] (Table 62.5).

Serum Cytokines and Muscle Damage Markers Taribian et al. [53] found that EPA and DHA supplement caused an inhibition in elevation of TNF-á and IL-6, which are inflammatory markers in the blood. Similarly we demonstrated that EPA and DHA ingestion reduced the levels of IL-6 (Fig. 62.1D) [21]. Furthermore, as a result of ingesting 0.36 g/day of EPA for 3 weeks, it has been reported that elevation of IL-6 was inhibited after four types of resistance training for the lower limbs [55]. Other studies have indicated that EPA and DHA ingestion can inhibit the elevation in levels of IL-6 and TNF-á after ECCs and

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TABLE 62.3  Summary of the Effects of EPA/DHA Supplementation on Delayed Onset Muscle Soreness References

Population (Age)

Dose (Per Day)

Duration

Exercise

Outcome

Houghton and Onambele [55]

17 healthy females (20.4 ± 2.3 y)

0.36 g of EPA

3 weeks

Resistance exercise (leg flexions, leg extensions, straight leg deadlifts, walking lunges; three sets of 10 repetitions at 70% 1RM)

Ineffective

Lembke et al. [49]

64 healthy, untrained males and females (more than the age of 18 y)

2.70 g of EPA and DHA

30 days

Elbow flexor eccentric contractions (two sets of 30 maximal efforts using the Cybex isokinetic dynamometer)

Effective

DiLorenzo et al. [56]

41 healthy, untrained males (21.8 ± 2.7 y)

2.0 g of DHA

4 weeks

Elbow flexor eccentric contractions (six sets of 10 Ineffective repetitions at 140% 1RM using dumbbells)

Lenn et al. [57]

13 males (22.7 ± 3.9 y) and 9 females (24.5 ± 5.5 y)

0.287 g of EPA and 0.194 g of DHA

30 days

Elbow flexor eccentric contractions (50 maximal efforts at 90 degrees/s using the Kin-Com dynamometer)

Ineffective

Gray et al. [58]

20 healthy, untrained males (23.0 ± 2.3 y)

1.30 g of EPA and 0.30 g of DHA

6 weeks

Knee extensor eccentric contractions (20 sets of 10 repetitions at 0.52 rad/s using the Biodex isokinetic dynamometer)

Ineffective

Tartibian et al. [52]

27 healthy males (33.4 ± 4.2 y)

0.324 g of EPA and 0.216 g of DHA

30 days

40-min bench stepping (knee height step, 50 cm on average, at a rate of 15 steps per minute)

Effective

Jouris et al. [48]

3 males and 8 females 2.0 g of EPA and (18–60 y) 1.0 g of DHA

2 weeks

Elbow flexor eccentric contractions (two sets to failure at 120% 1RM using dumbbells)

Effective

Tinsley et al. [54]

19 healthy, untrained females (22.5 ± 1.8 y)

3.60 g of EPA and DHA

2 weeks

Elbow flexor and leg extensor eccentric contractions (10 sets to failure at 50% 1RM using the elbow flexions and leg extension machines)

Effective

Tsuchiya et al. [21]

24 healthy, untrained males (19.5 ± 0.8 y)

0.60 g of EPA and 0.26 g of DHA

8 weeks

Elbow flexor eccentric contractions (six sets of maximal five repetitions at 30 degrees/s using the Biodex isokinetic dynamometer)

Effective

Ochi et al. [50]

21 healthy, untrained males (21.0 ± 0.8 y)

0.60 g of EPA and 0.26 g of DHA

8 weeks

Elbow flexor eccentric contractions (six sets of 10 repetitions at 40% 1RM, 30 degrees/s using dumbbells)

Effective

Phillips et al. [51]

40 healthy, untrained males (18–35 y)

0.80 g of DHA

2 weeks

Elbow flexor eccentric contractions (three sets of 10 repetitions at 80% 1RM using the arm curl machine)

Ineffective

Bloomer et al. [47]

14 recreational males (25.5 ± 4.8 y)

2.224 g of EPA and 2.208 g of DHA

6 weeks

60-min treadmill climb using a weighted pack (weight equal to 25% of body mass)

Ineffective

DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; RM, repetition maximum.

running exercise [47,51,53,56]. Thus EPA and DHA supplementation has a positive effect on inflammatory response after eccentric exercise. For more detailed discussion on the inflammatory response, including oxidative stress and immune function, one can refer to earlier reviews [18] (Table 62.6). Serum creatine kinase (CK) and myoglobin (Mb) are elevated by ECCs, which are typical skeletal muscle damage markers [16]. No consensus has been received regarding the inhibition of increases in CK and Mb with EPA and DHA ingestion. Taribian et al. [53] reported that EPA and DHA for 30 days are effective to reduce the CK and Mb after bench stepping. Meanwhile Gray et al. [58] demonstrated that after 1.30 g/day of EPA and 0.30 g/day of DHA daily for 6 weeks, there was no change in CK after knee exercise. We confirmed that there were no differences between groups in CK or Mb after ECCs (0.6 g/day of EPA and 0.26 g/day of DHA for 8 weeks) [21]. With regard to a single intake for DHA, 2.0 g/day for 4 weeks caused an inhibition of CK elevation [56], while 0.8 g/day for 2 weeks showed no change [51]. One possible reason for these inconsistent results for CK and Mb response is differences in exercise type and individual difference between subjects. It may be necessary to develop a new marker of muscle damage with little variation and to conduct verifications using it.

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TABLE 62.4  Summary of the Effects of EPA/DHA Supplementation on Range of Motion References

Population (Age)

Dose (Per Day)

Lembke et al. [49]

64 healthy, untrained 2.70 g of EPA and 30 days males and females DHA (more than the age of 18 y)

Elbow flexor eccentric contractions (two sets of 30 maximal efforts using the Cybex isokinetic dynamometer)

Ineffective

Lenn et al. [57]

13 males (22.7 ± 3.9 y) 0.287 g of EPA 30 days and 9 females and 0.194 g DHA (24.5 ± 5.5 y)

Elbow flexor eccentric contractions (50 maximal efforts at 90 degrees/s using the Kin-Com dynamometer)

Ineffective

Tartibian et al. [52]

27 healthy males (33.4 ± 4.2 y)

30 days

40-min bench stepping (knee height step, 50 cm on average, at a rate of 15 steps per minute)

Effective

Tsuchiya et al. [21]

24 healthy, untrained 0.60 g of EPA and 8 weeks males (19.5 ± 0.8 y) 0.26 g of DHA

Elbow flexor eccentric contractions (six sets of maximal five repetitions at 30 degrees/s using the Biodex isokinetic dynamometer)

Effective

Ochi et al. [50]

21 healthy, untrained 0.60 g of EPA and 8 weeks males (21.0 ± 0.8 y) 0.26 g of DHA

Elbow flexor eccentric contractions (six sets of 10 repetitions at 40% 1RM, 30 degrees/s using dumbbells)

Effective

0.324 g of EPA and 0.216 g of DHA

Duration Exercise

Outcome

DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; RM, repetition maximum.

TABLE 62.5  Summary of Effects of EPA/DHA Supplementation on Muscle Swelling References

Population (Age)

Dose (Per Day)

Duration

Exercise

Outcome

Tartibian et al. [52]

27 healthy males (33.4 ± 4.2 y)

0.324 g of EPA and 0.216 g of DHA

30 days

40-min bench stepping (knee height step, 50 cm on average, at a rate of 15 steps per minute)

Circumference; effective

Elbow flexor eccentric contractions (two sets to failure at 120% 1RM using dumbbells)

Circumference; ineffective

Jouris et al. [48] 3 males and 8 females (18–60 y)

0.20 g of EPA and 2 weeks 0.10 g of DHA

Tinsley et al. [54]

19 healthy, 3.60 g of EPA and 2 weeks untrained females DHA (22.5 ± 1.8 y)

Elbow flexor and leg extensor eccentric contractions Circumference; (10 sets to failure at 50% 1RM using the elbow ineffective flexion and leg extension machines)

Tsuchiya et al. [21]

24 healthy, untrained males (19.5 ± 0.8 y)

0.60 g of EPA and 8 weeks 0.26 g of DHA

Elbow flexor eccentric contractions (six sets of maximal five repetitions at 30 degrees/s using the Biodex isokinetic dynamometer)

Circumference; ineffective

Ochi et al. [50]

21 healthy, untrained males (21.0 ± 0.8 y)

0.60 g of EPA and 8 weeks 0.26 g of DHA

Elbow flexor eccentric contractions (six sets of 10 repetitions at 40% 1RM, 30 degrees/s using dumbbells)

Circumference; ineffective Cross-sectional area; ineffective

DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; RM, repetition maximum.

Neuromuscular Damage Previous studies have been shown that nerve dysfunction is also induced by rat ECCs [60]. Kouzaki et al. [45] reported that nerve conduction velocity (NCV) was decreased by 12%–24% from 1 to 2 days after human ECCs, and they suggested that this prolonged NCV was related to muscle strength deficit. The relationship between NCV and EPA and DHA has been investigated in an animal model [61]. Gerbi et al. [61] used diabetic rats to investigate the relationship between omega-3 intake, NCV, endoneurial edema, and axonal degeneration. They reported that EPA and DHA ingestion inhibited decreases in NCV in diabetic rats [61]. They proposed that EPA and DHA ingestion prevents membrane alteration and has Na, K-ATPase gene transcription effects [61]. Based on their results, we investigated whether EPA and DHA intake affects post-ECC NCV in humans [50]. Our results indicated that the supplementation of EPA and DHA daily for 8 weeks inhibited musculocutaneous nerve conduction latency after ECCs (Fig. 62.2). This observation can be assumed that EPA and DHA supplementation protects neuromuscular function, but further evidence is required around this field.

5.  MINERALS AND SUPPLEMENTS IN MUSCLE BUILDING

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EPA and DHA for Muscle Mass and Function

TABLE 62.6  Summary of Effects of EPA/DHA Supplementation on Serum Cytokines and Muscle Damage Markers References

Population (Age) Dose (Per Day)

Duration

Exercise

Outcome

Houghton and Onambele [55]

17 healthy females (20.4 ± 2.3 y)

0.36 g of EPA

3 weeks

Resistance exercise (leg flexions, leg extensions, CK; ineffective straight leg deadlifts, walking lunges; three sets IL-6; effective of 10 repetitions at 70% 1RM)

DiLorenzo et al. 41 healthy, [56] untrained males (21.8 ± 2.7 y)

2.0 g of DHA

4 weeks

Elbow flexor eccentric contractions (six sets of 10 repetitions at 140% 1RM using dumbbells)

CK; effective IL-6; effective

Gray et al. [58]

20 healthy, untrained males (23.0 ± 2.3 y)

1.30 g of EPA and 0.30 g DHA

6 weeks

Knee extensor eccentric contractions (20 sets of 10 repetitions at 0.52 rad/s using the Biodex isokinetic dynamometer)

CK; ineffective

Tartibian et al. [53]

45 healthy, untrained males (29.7 ± 6.6 y)

0.324 g of EPA and 0.216 g DHA

30 days

40-min bench stepping (knee height step, 50 cm on average, at a rate of 15 steps per minute)

CK; effective Mb; effective IL-6; effective TNF-á; effective

Tsuchiya et al. [21]

24 healthy, untrained males (19.5 ± 0.8 y)

0.60 g of EPA and 0.26 g of DHA

8 weeks

Elbow flexor eccentric contractions (six sets of maximal five repetitions at 30 degrees/s using the Biodex isokinetic dynamometer)

CK; ineffective Mb; ineffective IL-6; effective TNF-á; ineffective

Phillips et al. [51]

40 healthy, untrained males (18–35 y)

0.80 g of DHA

2 weeks

Elbow flexor eccentric contractions (three sets CK; ineffective of 10 repetitions at 80% 1RM using the arm curl IL-6; effective machine)

Bloomer et al. [47]

14 recreational 2.224 g of EPA and males (25.5 ± 4.8 y) 2.208 g of DHA

6 weeks

60-min treadmill climb using a weighted pack (weight equal to 25% of body mass)

CK; ineffective TNF-á; effective

CK, creatine kinase; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; RM, repetition maximum.

FIGURE 62.2  Changes (mean ± SD) in nerve conduction latency before (pre), immediately after (post), and 1, 2, 3, and 5 days after eccentric contractions in EPA group and placebo. *P < .05, a significant difference between the groups; †P < .05, a significant difference from preexercise value in the placebo group. DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; SD, standard deviation. Data are from Ochi E, Tsuchiya Y, Yanagimoto K. Effect of eicosapentaenoic acids-rich fish oil supplementation on motor nerve function after eccentric contractions. J Int Soc Sports Nutr 2017;14:23.

EPA AND DHA FOR MUSCLE MASS AND FUNCTION Muscle Mass Maintaining the skeletal muscle mass is important not only for athletes but also for common people from the viewpoint of sarcopenia. In the previous studies, muscle hypertrophy is evaluated by CSA of muscle belly and fiber, muscle thickness, growth factors and hormones, and protein metabolism (protein synthesis rate and insulin signaling pathway) [62–67]. Interestingly some previous findings have indicated that the ingestion of EPA and

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62.  EICOSAPENTAENOIC ACID AND DOCOSAHEXANOIC ACID IN EXERCISE PERFORMANCE

DHA may inhibit a decrease in muscle mass with animal model [68–71]. Previous studies showed that omega-3 ingestion activated the Akt-mammalian target of rapamycin (mTOR)-p70S6K pathway, which is extremely important in protein synthesis, in an animal experiment [68,71]. In addition, an investigation using dystrophin-deficient mouse found that EPA and DHA intake increased the number of activated satellite cells [72]. Similarly Wei et al. [70] also confirmed that DHA-enriched diet caused increases in insulin-like growth factor 1 (IGF-1) mRNA expression, Akt-mTOR-p70S6K pathway, and the fractional synthesis rate in pigs. The mechanism(s) of EPA and DHA for IGF-1, its signals, and satellite cells is mostly unknown. It is speculated that unknown signal cascades that affect macrophages, the nuclear factor-kappa B, and membrane lipid composition may be involved [72]. Interestingly Wei et al. [69] reported that the EPA increases phosphorylation of mTOR underlying stress conditions, whereas it did not affect under physiological conditions. Thus it appears that certain evidence has been obtained regarding effects of EPA on maintaining the skeletal muscle in animals under wasting condition, but verification in humans is required. Meanwhile the effects of EPA and DHA supplementation on muscle mass in humans are limited. Smith et al. [73] reported that mTOR signals with hyperaminoacidemic-hyperinsulinemic clamp and muscle protein fractional synthesis rate increased after 1.86 g/day of EPA and 1.50 g/day of DHA for 8 weeks in nine subjects (men and women aged 25–45 years). They found that supplementation of 1.86 g/day of EPA and 1.50 g/day of DHA for 6 months to 44 elderly subjects (omega-3; n = 40, control; n = 20, men and women aged 60–85 years) caused an increase in thigh muscle mass, suggesting that this could be a new therapy for preventing sarcopenia [74]. However, these results are not consistent with the results of training experiments [75]. McGlory et al. [75] found that 3.5 g/day of EPA and 0.9 g/day of DHA supplementation for 8 weeks did not change myofibrillar muscle protein synthesis and decrease protein synthesis before and after high-intensity exercise in 20 trained men (21–24 years). They discussed that these discrepancies were due to the differences in the (1) method of the protein synthesis rate, (2) method of amino acid administration, and (3) training experience of subjects. In addition to these points, I suggest that the difference of gender, age, dose, and period may have influenced the results. Da Boit et al. [76] investigated the effect of 2.1 g/day of EPA and 0.6 g/day of DHA for 12-week intake in elderly individuals (men: 70.6 ± 4.5 years, women: 70.7 ± 3.3 years). They found no effects on results such as muscle CSA, myofibrillar muscle protein synthesis rate, or p70s6k after resistance training (twice per week). In summary the role of EPA and DHA in muscle mass with training is unclear based on the previous human results, but the evidence demonstrates positive effects under wasting condition.

Muscle Function Previously muscle function is evaluated by static and dynamic torque, 1RM, rate of torque development (RTD), electromyography (EMG), electrical mechanical delay (EMD), and short physical performance tests such as balance and walking. As mentioned previously, Smith et al. [74] confirmed not only increased thigh muscle mass but also increased handgrip strength and 1RM squats with 1.86 g/day of EPA and 1.50 g/day of DHA for 6 months in 44 elderly individuals (60–85 years). In addition, Lewis et al. [77] investigated acute training response in young trained men who ingested 0.375 g/day of EPA and 0.51 g/day of DHA for 21 days. From the results, they reported that the ingestion of EPA and DHA increased vastus lateralis EMG compared with placebo. Rodacki et al. [78] divided elderly women (45 women, age: 64 ± 1.4 years) into three groups and investigated the relationship between ∼0.4 g/ day of EPA and 0.3 g/day of DHA intake and training effects over 12 weeks. One group performed resistance training only for 90 days, but the other groups performed the same training with EPA and DHA supplementation for 90 or for 150 days (supplemented 60 days before training). The results showed that peak torque, RTD, EMG, and EMD improved significantly in supplemental groups. Da Boit et al. [76] demonstrated that 2.1 g/day of EPA and 0.6 g/day of DHA for 18 weeks and muscle resistance training caused increases in maximal isometric torque of knee extensors, maximal isometric torque of knee extensor per CSA, in elderly women, but not in elderly men. Thus in terms of muscle function it can be possible to conclude that EPA and DHA are effective for neuromuscular adaptation after training. One possible mechanism for this effect is an increase in the incorporation of omega-3 fatty acids in the cells, particularly in the nervous system and muscles [79], which results in improvement in the fluidity of the membrane and acetylcholine sensitivity [18,78,80,81]. The exact biological mechanisms underlying the beneficial effect of EPA and DHA on muscle and neuron are unknown, but EPA and DHA appear to play important roles in these adaptations. Further research is required to elucidate the effect of EPA and DHA for neuromuscular adaptation with training.

5.  MINERALS AND SUPPLEMENTS IN MUSCLE BUILDING

References

725

SUMMARY AND FUTURE DIRECTIONS Summary The main points of this review can be summarized as follows.

  

1. N  o consensus has been reached regarding whether intake of EPA and DHA is effective for increasing VO2max, while EPA and DHA may improve exercise economy and perceived exertion during exercise. 2. EPA and DHA improve cardiovascular function at rest and have positive effects on HR, stroke volume, and cardiac output during submaximal exercise. 3. Some positive effects of EPA and DHA have been observed in ECC-induced muscle and nerve damage, while some results are not consistent. 4. EPA and DHA may have positive effects on muscle mass under wasting condition, but it is unclear under training situation. 5. EPA and DHA have positive effects on muscle function, especially for neuromuscular adaptation.   

As mentioned previously, it can be conclude that EPA and DHA have several positive roles in exercise performance. Unfortunately currently there is no clarified optimal period and dose for EPA and DHA. Therefore it will be necessary to investigate appropriate conditions taking age, sex, exercise experience, diseases, and so forth into account. It showed that 30- to 60-day ingestion is needed to result in uptake by the human myocardial membrane [59], and ingestion of 3–4 months increased red blood cell deformability in patients with angina and claudication [82,83]. Regarding the dose, it should be noted that the amount of EPA and DHA is limited to a total of 3 g/day for safety in humans by the Natural Medicines Comprehensive Database [84]. Simopoulos [85] mentioned that the majority of athletes, especially at the leisure level, should diet EPA and DHA of about 1–2 g/day as a general guideline. Otherwise it has been suggested that an ingestion ratio of EPA to DHA of approximately 2:1 may be beneficial in counteracting exercise-induced inflammation and for the overall health of an athlete [20,85]. In particular the ingestion of single EPA or DHA did not elicit attenuation in several muscle damage markers. Hence I speculate that EPA and DHA might have mutually complementary roles, and thereby simultaneous ingestion of EPA and DHA has a possible synergistic effect. In the future the ingestion period, dose, either EPA or DHA, or the synergistic effects of the simultaneous ingestion of both need to be investigated in other interventions including muscle damage. Interestingly it has been found that EPA and DHA cause the muscle fiber transition from type IIb to IIx in fast-type dominant muscle [86] and were effective against lipid metabolism such as peroxisome proliferator–activated receptors, brown adipocytes mitochondria, and uncoupling protein-3 [87,88]. These findings may constitute basic data that could be useful for not only improving sports performance but also improving clinical conditions and promoting health. In the future I hope that these data will form a starting point for further research into this field.

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5.  MINERALS AND SUPPLEMENTS IN MUSCLE BUILDING