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Phosphatidylserine for the Athlete

Carter, Jeremy MS, CSCS; Greenwood, Mike PhD, CSCS*D, RSCC*D, FNSCA

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Strength & Conditioning Journal: February 2015 - Volume 37 - Issue 1 - p 61-68
doi: 10.1519/SSC.0000000000000112
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Abstract

INTRODUCTION

Overtraining syndrome (OTS) is an unwanted training effect that occurs with inadequate recovery for the training stimulus. OTS has several negative detriments to the body and can deleteriously impact the physiological, biochemical, immunological, and psychological systems of the body (4). The negative outcomes of OTS can affect athletes of all levels of competition by impairing recovery and performance. Although the causes of OTS are multifaceted, those who are most susceptible to OTS include those with low stress capacities, have long or multiple competitive seasons, have training program design flaws (i.e., abrupt increases in volume-load), acquire insufficient sleep, have poor nutrition, have previously experienced an episode of OTS, participate in endurance sports, and those with high amounts of additional nonexercise stress in their life (4).

Currently, there are no agreed-upon markers or methods to diagnose OTS (4). An athlete in training will always be along the continuum of OTS ranging anywhere from acute fatigue, functional overreaching, nonfunctional overreaching, or OTS, with the distinguishing factor among them being the amount of time necessary to recover (4). The literature has shown that depending on the severity of the OTS, it may take months to years to fully recover (28,32). The strength coach should be mindful of preventing nonfunctional overreaching or OTS, since they are associated with impairments to the physiological, biochemical, immunological, and psychological systems of the body, as well as reduced performance (4). To reduce the likelihood of OTS, the strength coach should take several steps to reduce the possibility of the development of OTS, including the possible use of appropriate dietary supplements (4).

One supplement that can potentially enhance restoration is phosphatidylserine (PS). Research on PS shows it has unique properties reducing cortisol levels after exercise (8,11,29,30,36), which would lead to an improved testosterone to cortisol ratio (36). Furthermore, research on PS has shown it to enhance mood, performance, recovery, immunity, decision making, accuracy, and cognition (8,11,18,19,24,33). The purpose of this article is to discuss PS, review the literature on the supplement PS, and describe which population might benefit most from its supplementation.

PHOSPHATIDLYSERINE

PS is a naturally occurring phospholipid that is found in the inner layer of cell membranes and is essential for cell integrity (15,17,29,30,36). Phosphatidyl phospholipids, such as PS, consist of 2 fatty acid groups that are connected though a glycerol backbone to a phosphate ester group (15,17). PS has the amino acid L-serine attached its phosphate ester group (26) and is found in the highest concentration in organs with a high metabolic demand (i.e., heart, lungs, brain, liver, and skeletal muscle) (36). According to Jäger et al. (15), “PS is most concentrated in the brain where it comprises 15% of the total phospholipid pool.” Jäger et al. (15) also state that the ratio for PS in the phospholipid pool for the lungs is 7.4%, testes 6.4%, kidneys 5.7%, liver 3.8%, skeletal muscle 3.3%, heart 3.2%, and blood plasma 0.2%.

PS is needed for enzyme cofactors, cellular structure/regulation, and has diverse effects on the body such as improved exercise recovery, attenuated delayed onset muscle soreness, improved immune function, increased mental acuity, increased mental energy, accelerated loss of adipose tissue, potential antioxidant functions, necessary for enzyme cofactors, initiates cell phagocytosis through apoptosis signaling, and improved cell integrity (8,15,17,21,24,40), as well as the possible ability to prolong exercise time to exhaustion (18,19). One unique attribute to PS is its ability to blunt cortisol (8,11,29,30,36), thus improving the testosterone to cortisol level (36), and providing a favorable hormonal status for training individuals. Since cortisol has been associated with weakening the immune system, impairing cognition, lowering testosterone, and facilitating OTS (2,4,20,31), the use of PS could be applicable for the athletic population, especially for those who are prone to or who have had an episode of OTS.

Earlier studies on PS implemented bovine PS (B-PS). However, due to the risks of transmitting mad cow disease, B-PS derived from cows has been replaced with a derivative of soybeans (S-PS) (15). The soybean version of PS is commercially available with dosages ranging from 100 to 500 mg (15). Recently, there has been research (22) on PS derived from krill (K-PS). The International Society of Sports Nutrition (ISSN) recommends supplementing with 800 mg/d of PS as a post-workout intervention (24). PS can be obtained through a diet that is high in cholesterol and includes food such as whole eggs, meat, and internal organs (15). Since the body can synthesize PS through natural processes by scavenging phosphatidylcholine or phosphatidylethanolamine, Kingsley (17) suggests that PS “may not qualify as an ‘essential’ nutrient.” However, the average Western diet only consists of approximately 130 mg/d of PS, with a diet high in animal protein providing more PS compared with a vegetarian diet (180–50 mg/d) (13). Furthermore, many athletes and coaches fear high consumptions of saturated fat and cholesterol. Therefore, it seems prudent to further research PS on various populations using different dosages and research designs for the athlete.

BOVINE PHOSPHATIDYLSERINE AND EXERCISE

As mentioned, earlier studies on PS implemented B-PS. However, due to the risks of transmitting mad cow disease, B-PS derived from cows has been replaced with a derivative of soybeans. Monteleone et al. (30) studied the effects of B-PS on cortisol, adrenocorticotrophic hormone (ACTH), growth hormone (GH), prolactin (PRL), blood glucose, blood lactate, blood pressure (BP), and heart rate (HR) response in reaction to a bicycle ergometer protocol. The subjects (non–physically active men) supplemented for 10 days with a placebo, 400 mg/d of B-PS, and 800 mg/d of B-PS in a double-blind crossover design study. The researchers concluded that 800 mg/d of B-PS blunts the rise in cortisol and ACTH from exercise, whereas 400 mg/d of B-PS did not affect the levels of cortisol produced from a standardized exercise protocol (note that due to technical difficulties, no data are available on ACTH after the 400 mg/d intervention). Both the 400 and 800 mg/d of B-PS supplementation had no effect of GH, PRL, BP, HR, blood glucose, and blood lactate.

SOYBEAN PHOSPHATIDYLSERINE AND EXERCISE

Starks et al. (36) studied the effects of 600 mg/d of S-PS on 10 males who performed 15 minutes of cycling after supplementing with a placebo or S-PS for 10 days. The authors used a double-blind, placebo-controlled, crossover design with no washout period. Cortisol, testosterone, lactate, and GH, were assessed 30 minutes before exercise, immediately before exercise, after the 15-minute cycling protocol, and at 20, 30, 40, 60, and 80 minutes from the start of exercise. The experimental trial (600 mg/d of PS) produced significantly lower resting cortisol levels before exercise, whereas resting testosterone (p = 0.20) and resting GH (p = 0.30) levels were not significantly altered. When investigating the area under the curve analysis, the S-PS trial significantly decreased cortisol, increased testosterone, and elevated testosterone to cortisol levels when compared with the placebo trial. Similar to other studies, the authors found no difference in lactate and GH concentration from PS (29,30). Therefore, the authors concluded that 600 mg/d of PS supplemented for 10 days promotes a favorable hormonal status for training individuals.

Parker et al. (33) examined the effects of 400 mg/d of S-PS supplemented over 14 days on 18 lower-body resistance-trained males using a randomized, double-blind, placebo-controlled, crossover design without a washout period. The investigators measured cognitive performance, mood, and endocrine response (cortisol and testosterone) before and after a lower-body resistance training session involving 5 sets of 10 repetitions at 70% of their 1 repetition maximum using the squat, leg press, and leg extension exercise (the researchers noted an 87% increase in plasma cortisol during pilot work for the study). Before exercise, S-PS supplementation reduced the time needed for correct calculation using a serial subtraction test by 20%, improved the amount of correct calculations by 13%, and decreased the total amount of errors by 39%. The 400 mg/d of S-PS did not affect cortisol, testosterone, or mood before or after the exercise bout, nor did it improve cognitive function using the serial subtraction test after exercise. Monteleone et al. (30) also found that supplementing with 400 mg/d of PS for 10 days did not affect cortisol levels. Based on the findings of Monteleone et al. (30) and Parker et al. (33), 400 mg/d of PS supplemented for 10–14 days may be inadequate to blunt the rise in cortisol from exercise. It may be necessary to either use higher dosages (i.e., 800 mg/d of PS) or to load for longer durations (i.e., >14 days) to receive benefits from PS in regards to the blunting of cortisol induced by exercise.

For example, using a balanced order, double-blind, crossover design research, Fahey and Pearl (8) showed that 800 mg/d of S-PS supplemented for 2 weeks decreased postexercise cortisol level for 11 resistance-trained males compared with the placebo. The subjects engaged in a vigorous weight training program for 2 weeks involving 4 full body weight training sessions per week with each session involving 5 sets of 10 repetitions for 13 different exercises. The vigorous 2-week training protocol was separated by a 3-week recovery/washout period and then repeated with the subjects either consuming the 800 mg/d of S-PS or a placebo during the 2 phases of training. Fahey and Pearl (8) had a unique research design due to the fact that the subjects loaded on the S-PS during the intense training. As a result, there were no significant differences between the placebo and S-PS trials during the first part of the training. However, as the subjects near the end of the training period, the S-PS was able to suppress cortisol levels after exercise. Although the S-PS did not lower the ACTH levels, it did prevent the subjects' ACTH levels from increasing, whereas in the placebo group, the ACTH levels increased as the training period continued. Fahey and Pearl (8) noted no significant difference between the trials for creatine kinase, testosterone, luteinizing hormone, waking HR, body mass, lean body mass, or percent body fat. However, the S-PS did significantly reduce delayed onset muscle soreness and improved the subjects' perception of well-being.

Kingsley et al. (18) studied the effects of 750 mg/d S-PS supplemented for 10 days on 14 recreationally active males. The study (double-blind nonrepeated measures) assessed the exercise capacity, neuroendocrine function, oxygen uptake, kinetic response, and perceived feeling states during and immediately following intermittent cycling. The cycling protocol had three 10-minute stages at 45, 55, and 65% of the subjects' V[Combining Dot Above]O2 max, followed by the final stage at 85% of their V[Combining Dot Above]O2 max in which the subjects rode to exhaustion. The main finding of the study was that the S-PS group increased their ride time to exhaustion by 2:00 ± 0:28 minutes:seconds compared with the placebo group, which had similar ride times for the first and second trial. The supplemental protocol had no effect on the oxygen kinetics, fuel utilization, serum cortisol levels, and feeling states when compared with the control group. Compared with other research (8,11,29,30,36) that showed PS to significantly lower serum cortisol levels after physical exercise, there was no difference between these 2 groups. The researchers suggest this could be due to the fact that the S-PS group rode longer at 85% of their V[Combining Dot Above]O2 max compared with the control group.

An additional study by Kingsley et al. (19) studied the effects of 10 days of 750 mg/d S-PS supplementation compared with a placebo on 16 male soccer players. The investigators measured cortisol, oxidative stress, muscle damage, and perceived soreness before a simulated soccer match, as well as 15 minutes, 24 hours, and 48 hours following the running protocol. During the exercise protocol, HR, rate of perceived exertion, blood lactate, and run time to exhaustion were measured. The S-PS increased the pre- and post-exercise concentration of the antioxidant γ-tocopherol, with no effect on any other measured antioxidants (i.e., vitamin C, retinol, β-carotene, and α-tocopherol). The S-PS did not affect the measures of muscle damage (i.e., myoglobin and creatine kinase concentration), the subjects' cortisol levels, or the measures of oxidative stress (i.e., lipid peroxidation) when compared with the placebo. In agreement with additional research (11,29,30,36), PS seems to have no effect on HR or blood lactate. Although not statistically significant (p = 0.084), S-PS tended to increase run time to exhaustion. This is similar to the previously mentioned study by Kingsley et al. (18) who showed S-PS to significantly increase the subjects' cycling time to exhaustion. Once again, it seems that longer ingestion protocols (i.e., >14 days) may be necessary to significantly reduce cortisol levels after exercise.

Therefore, perhaps 1 unique trait of PS is to improve endurance performance by increasing time to exhaustion as evident by the research of Kingsley et al. (18,19). Research using rodents (9,23) and humans (37) suggests that endurance exercise decreases the PS concentration in skeletal muscle fibers (9,23), the muscle fibers of the diaphragm (9), and erythrocytes in the blood (37). In his review, Kingsley (17) suggests that PS may increase endurance activities by maintaining an optimal calcium ionic balance at the sarcoplasmic reticulum, thus delaying fatigue. Therefore, further research is warranted regarding the ability of PS to improve time to exhaustion. Furthermore, considering that OTS and immune suppression are observed more in endurance athletes (4), PS supplementation may benefit this population since it seems that exercise decreases PS concentration (Table).

Table Exe
Table Exe:
rcise and chronic phosphatidylserine usage in humans

PRE-EXERCISE PHOSPHATIDYLSERINE

The ISSN suggests that PS be used as a post-workout supplement due to its anticatabolic nature, as well as its effects on lowering cortisol and ACTH (24). The ISSN cautions the use of PS for pre-exercise purposes, since it may mitigate the anabolic cascade due to the reduced catabolic input (24). However, research (29) has been done using PS as a pre-workout supplement. Monteleone et al. (29) studied the effects on B-PS on plasma epinephrine (EPE), norepinephrine (NE), dopamine, ACTH, cortisol, GH, PRL, BP, HR, and glucose. The 8 non–physically active male subjects performed 3 standardized bouts of exercise either using a placebo (100 mL of saline), 50 mg of B-PS, or 75 mg of B-PS that was administered intravenously 10 minutes before exercise. The authors demonstrated that both the 50 and 75 mg doses of B-PS administered intravenously 10 minutes before exercise significantly lowered the cortisol and ACTH response to exercise with the 75 mg dose having a greater effect. Although not significantly significant, there was a trend for the PS to lower NE and EPE, whereas GH and PRL levels were not affected by any treatment (note that GH and PRL had high intersubject variability). It should be noted that exercise performance was not a dependent variable.

A study by Hoffman et al. (12) involved the use of an S-PS containing supplement using an acute protocol (trial 1) containing 50 mg of PS before testing reaction time, anaerobic power, subjective measures of alertness, energy, fatigue, and focus on 17 male and 2 female college students. After the acute ingestion (trial 1) of the supplement, the subjects either consumed a placebo or the PS containing supplement for 4 weeks and repeated the same testing protocol (trial 2). The authors found positive benefits in focus, alertness, and reaction time during trial 1, whereas the supplement provided no greater benefits during trial 2. However, the authors are unable to conclude the magnitude of S-PS (50 mg) on the effects of the subjects because each serving of the supplement also contains: α-glycerophosphocholine (150 mg), choline bitartrate (125 mg), niacin (vitamin B3; 30 mg), pyridoxine HCL (vitamin B6; 30 mg), methylcobalamin (vitamin B12; 0.06 mg), folic acid (4 mg), L-tyrosine (500 mg), anhydrous caffeine (60 mg), acetyl-L-carnitine (500 mg), and naringin (20 mg). The researchers (12) suggest that it is possible that some habituation occurred during the chronic supplementation, which would explain the lack of its effect on trial 2.

NONEXERCISE PHOSPHATIDYLSERINE

As noted earlier, PS has other potential unique abilities for athletes besides its anticatabolic effects of reducing cortisol and ACTH. When ingested, it seems that exogenous PS has the ability to cross the blood brain barrier, where it has a dramatic effect on the hypothalamus. PS has been shown to improve cognition in the elderly (6,7), those who suffer from Alzheimer's disease (10), and individuals with depression (25). PS seems to have the ability to increase glucose in the brain without needing a rise in blood glucose (3). Since the brain can only use glucose as a fuel source, PS might be beneficial for athletes who are prone to glycogen depletion. Furthermore, combining PS with omega-3 fatty acids has been shown to reduce the symptoms of attention-deficit hyperactivity disorder in children (26). As mentioned, some research (22) has used K-PS. One unique trait of K-PS compared with S-PS is that K-PS will contain the omega-3 fatty acids docosahexaenoic acid (commonly known as DHA) and eicosapentaenoic acid (commonly known as EPA). Lee et al. (22) showed that both K-PS and S-PS improved the spatial working memory, prevented cell loss in the hippocampus region of the brain, and increased choline acetyltransferase and acetylcholinesterase in the hippocampus region in aged male rats.

PS may improve cognition for several reasons, such as increased brain glucose supply, improved cholinergic function in the brain, and improved membrane potential, function, and fluidity (3,5,22,35,39). Although the athlete will most likely not have impaired memory compared with the geriatric or diseased populations, memory is still a crucial factor in human performance, especially for the athlete with high amounts of additional stress, as well as those who obtain minimal sleep. The lack of sleep coupled with high amounts of stress can decrease performance and increase cortisol. High cortisol levels can impair restoration, lower testosterone levels, promote OTS, weaken immunity, and hinder cognition (2,4,20,31). Therefore, PS supplementation has the potential to enhance athletic performance on several fronts, especially for the athlete who has high amounts of additional stress.

Research involving 48 male undergraduate students with neuroticism who supplemented with 300 mg/d of S-PS (average of 1 mg of PS per 0.55 pound of body weight) showed that subjects who supplemented with S-PS (n = 22) decreased feelings of being stressed after performing a demanding arithmetic task compared with the placebo group (n = 26) (1). Jäger et al. (14) showed that 42 days of S-PS (200 mg/d) in the form of a nutritional bar increased the accuracy of male golfers, as well as produced a trend (p = 0.07) for improving perceived stress levels when compared with the placebo. The ability of PS to improve the motor abilities of golfers has potential to benefit the accuracy in other athletic competitions as well, or potentially the military population.

Hellhammer et al. (11) studied the effects of a soy lecithin phosphatidic acid and S-PS complex supplement (PAS) on pituitary adrenal reactivity (i.e., cortisol and ACTH), HR, and psychological response after the Trier Social Stress Test, which involves public speaking and an arithmetic task. The PAS supplement consisted of 100 mg of S-PS, 125 mg phophatidic acid, and 270 mg of additional inert phospholipids per capsule. The researchers divided the 80 subjects into 4 equal groups consisting of 10 males and 10 females. The subjects were divided so that each group was from the same socioeconomic status. The subjects were randomly placed in a placebo, 400, 600, or 800 mg/d PAS group. After 4 weeks of supplementation, the researchers noted that all 3 PAS experimental groups significantly lowered their ACTH, cortisol, and psychological stress, with no effect on HR. Hellhammer et al. (11) noted that an increase in dosage had less effects on the stress response as evident by no significant differences among the supplemental groups.

PRACTICAL APPLICATIONS

Based on our review of the literature, it seems that similar to creatine or beta-alanine, a loading period is needed for PS to have positive effects. Also, similar to creatine and beta-alanine, there seems to be a point of diminishing returns in regards to continual usage of higher dosages. Further research is needed on PS to determine the optimal dosage for the loading and maintenance period, as well as establish the washout period. If a primary goal is to seek rapid results from PS supplementation, the athlete should use higher dosages (i.e., 800 mg/d), whereas lower dosages (i.e., 100–300 mg/d) will most likely provide similar effects over a longer time period. Jäger (13) suggests using 300 mg/d of PS for 1–2 months, followed by a maintenance phase of 100 mg/d. However, Jäger (13) was referring to the cognitive benefits of PS, and not PS's ability to blunt cortisol. To the best of our knowledge, no study we referenced caused negative side effects of ingesting PS. However, mega-dosing of any nutrient is not recommended nor is it healthy. Furthermore, any individual who is on prescribed medication from a medical physician should consult with their health care professional to ensure that exogenous supplemental PS does not interfere with their medication(s).

Based on our readings, a loading phase of 800 mg/d over 2–3 weeks, followed by a maintenance phase (i.e., 200–400 mg/d) may be optimal for the athlete. However, more research is needed for stronger conclusions. The athlete can either ingest PS as a post-workout intervention, before going to sleep, or on waking up, since cortisol levels heighten overnight (27). Furthermore, the athlete can break up the dosage throughout the day. For example, half their dose could be ingested after workout, and half their dose be ingested before going to sleep, or on waking depending on their workout time. Whether or not 1 dose or multiple dosages of equal quantities of PS throughout the day is more beneficial is yet to be determined. However, we the authors feel that as long as PS is not ingested before a workout, equal quantities of PS per day would provide similar benefits throughout a training period.

The ability of PS to blunt cortisol and ACTH is probably related to its effect on the hypothalamus. An individual's cortisol level was previously thought to reflect OTS. However, now it is suggested that cortisol is not reflective of OTS, but rather an immediate picture of the physiological strain of an athlete (34). Lately, research using hair cortisol has been suggested to show the longitudinal stress of an individual (34). Therefore, future research on PS should include hair cortisol as a measure of chronic stress to obtain a better picture of the effects of PS.

The athletes who will benefit most from supplemental PS are individuals who (a) have high amounts of additional nonexercise stress, (b) have reoccurring illnesses, (c) have a low stress capacity, (d) are prone to OTS or have experienced an episode of OTS, (e) are likely to become glycogen depleted, (f) engage in high volumes of aerobic training, (g) are vegetarian/vegan, (h) have a poor diet, (i) participate in additional sports or training, (j) engage in long or multiple competitive seasons, and (k) those who do not acquire enough sleep.

Individuals' cortisol response varies greatly to a provided stimulus (31). Therefore, individuals with lower stress capacities will have greater benefits from PS supplementation, especially if they have high amounts of life stress. Aerobic athletes are at a greater risk of developing OTS (4), and it seems intense exercise depletes the body's stores of PS (9,23,37). Furthermore, individuals who have experienced an episode of OTS are more likely to experience another episode compared with people who have never reached OTS (28).

As mentioned, PS can be obtained through a diet containing cholesterol (15). Therefore, vegetarians and vegans will consume less PS compared with those who eat meat. Thus, PS might be optimal for the vegetarian/vegan athlete. Intense exercise can override the antioxidant defense resulting in lipid peroxidation due to the excess in free radicals produced (19). Therefore, athletes who have a poor diet could lack adequate antioxidant intake, or those who have reoccurring illnesses could benefit from the proposed antioxidant benefits of PS.

The lack of sleep impairs cognitive function due to the alterations in the neurotransmitters, as well as oxidative damage (16). It is estimated that acetylcholine's turnover rate is 10-fold higher than other neurotransmitters in the brain (13). PS has been shown to enhance the activity of acetylcholinesterase (22). Furthermore, PS has been shown to facilitate glutamatergic neurotransmission and dopamine release, thus enhancing cognitive function, memory, and learning (13). Therefore, PS may be especially beneficial for the military population. Considering that soldiers performing combat missions typically acquire a low amount of sleep, have high volumes of stress, and in many cases are in a caloric deficit, the potential for PS to lower cortisol, increase testosterone, improve the testosterone to cortisol ratio, increase the supply of glucose to the brain without exogenous glucose supplementation, enhance cognition, act as an antioxidant, improve accuracy, facilitate recovery, enhance cellular integrity, increase time to exhaustion, and strengthen the immune system is worth investigating. Furthermore, the washout for PS remains unknown. Therefore, PS could provide benefits even after ending exogenous ingestion. Research (38) on the military population has shown that individuals who have higher testosterone levels before starting an 8-week training cycle are able to sustain the accumulation of stress better than those with lower resting testosterone levels.

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Keywords:

phosphatidylserine; overtraining; supplement; restoration

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