by Thomas Incledon, PhD(c), RD, LD/LN, RPT, NSCA-CPT, CSCS
Why you should read this article
Everyone wants to put on muscle. Whether your reasons are to look better, play better, or some combination of the two, adding skeletal muscle can help you achieve those goals. One supplement that you may want to try is phosphatidylserine (or phosphatidyl-serine or PS). In theory this supplement has the potential to positively affect important hormones that can help you to put on muscle. During the course of this article, I will educate you on what it is, how it could work, the dosages used in scientific studies, additional benefits, and the potential side effects. Read the whole article before you go out and buy a ton of this stuff and then find out you may not need it.
What’s the background on phosphatidylserine?
Phosphatidylserine is a glycerophospholipid. This family of compounds includes cephalin (phosphatidylethanolamine) and lecithin (phosphatidylcholine). They have a structure similar to triglycerides (glycerol backbone with three fatty acids attached to it). The difference is that PS has a phosphate and serine group attached to the third carbon on the molecule. Please see Figure 1. You should realize that the chain lengths (number of carbons) of the fatty acids (R1 and R2) on the first and second carbon positions can vary. This means that PS is not one specific chemical structure but a whole bunch of structures. Its analogous to saying you have an apple and I ask if it is a Red Delicious or MacIntosh. Both are still apples yet they are different. With PS you can have some species with shorter chain fatty acids and other species with longer chain fatty acids. Generally speaking, the PS with longer chains of fatty acids must be derived from animal sources such as bovine cortex (yes this is cow brain). This is referred to as bovine cortex derived phosphatidylserine (BCPS). PS with shorter chain of fatty acids can be derived from soybeans and therefore may be called soy lecithin derived phosphatidyl serine (SLPS).
The question you should be thinking at this point is:, Do both of these versions of PS work the same? As a scientist you learn very quickly not to make a hasty decision. Most studies were done using BCPS. The supplements sold through health food stores and muscle magazines are SLPS. These are two different products. Before this summer when clients asked me if they should take the SLPS I said no. My rationale was that the molecular species was different from BCPS, there was very little information available, and my clients don’t pay me to waste their money. I now feel that SLPS may have a role in the supplement regime of my athletes. This past summer, some research was presented at the American College of Sports Medicine Annual Meeting (ACSM) (1). The research dealt with the effects of SLPS on hormonal responses in resistance trained males. I will go over this in more detail but first lets cover some basic endocrinology so you can see how and why this may help and then you can make your own decision if you need it or not.
Cortisol production
Cortisol is a steroid hormone that is produced by the adrenal glands. Its stimulation is dependent upon a system referred to as the hypothalamic-pituitary-adrenal axis (HPA). See Figure 2. The hypothalamus is stimulated by stress to release corticotrophin releasing factor (CRH). CRH in turn stimulates the anterior pituitary to release adrenocorticotropin hormone (ACTH). ACTH then stimulates the adrenal glands to produce cortisol. In people with a normal functioning HPA axis, excess levels of ACTH or cortisol inhibit additional production of cortisol. This serves as a control for the body and prevents cortisol levels from becoming too high.
Cortisol is also a glucocorticoid and is catabolic. This means that it takes proteins, amino acids, and fatty acids and breaks them down into smaller molecules that can be used to produce glucose, which is an important energy source for the body. Cortisol gets a bad rap because it does stimulate the breaking down of skeletal muscle. That is only half the story though. If you lose the ability to produce cortisol you don’t magically gain muscle. In fact people that don’t produce any cortisol have less muscle and can even die (2). The point here is that cortisol is necessary. The concern with high levels of cortisol is that skeletal muscle may be broken down and converted into glucose. With resistance exercise there is a protective effect imparted to your muscles that prevents cortisol from working as effectively. It may be that lifting weights attenuates the ability of cortisol to bind to proteins in your muscle cells called receptors. Since muscle is bombarded all day long by anabolic hormones like testosterone and insulin and catabolic hormones like cortisol, the hormonal environment that the cell is exposed to can have serious consequences on muscle growth. Even though weight training may prevent cortisol from doing some of its work, if cortisol levels are high enough chronically then muscular gains will be compromised. An ideal situation would be to elevate testosterone (an anabolic hormone) and lower cortisol (a catabolic hormone). This is where PS comes in because it can do both!
In one study, 11 weight-trained men were exposed to a placebo condition and a treatment condition. During the placebo condition they received something that should not have induced any changes in hormonal levels, while during the treatment condition they received 800 mg of SLPS per day. The subjects performed 5 sets of 10 reps of 13 exercises, four times a week for 2 weeks. This protocol was followed for both treatment conditions. After six days of supplementation, cortisol levels decreased when the guys were taking PS. Testosterone increased over the first week of PS treatment and then declined during the second week. These results were in agreement with earlier work (2,3) which showed BCPS could decrease ACTH and cortisol levels. What I like about this recent study is that there was almost a 50% reduction in cortisol and a 30% + increase in testosterone during the times described above. This could be interpreted as the anabolic environment improving to favor muscle cell growth. Your hard working muscles can grow faster in an anabolic environment.
Just so that you get the whole story, let me point a few things out. When discussing the hormonal responses associated with exercise, most people will see an increase in testosterone or a decrease in cortisol and say this is better for performance. This is based off of studies showing relationships between testosterone:cortisol ratios and performance (4). You must be aware that no study has actually manipulated this hormonal ratio and studied the effects on performance. The fact that relationships have been published in the literature does not mean this ratio is the final say. Also in terms of availability of a hormone to bind to tissues and do its job, both testosterone and cortisol have free forms (not bound to proteins) that circulate in the body. The free forms are much more bioactive than their protein bound counterparts. None of the studies on PS have measured the free forms of these hormones. This is not usually a big deal because if there is a certain percentage increase or decrease in these hormones then a similar percentage is found in the free fraction. Without measuring it we must assume this is what happened, and in most cases it is a safe assumption to make.
Other benefits of PS
Another benefit regarding PS supplementation includes improved well being and lower ratings of muscle soreness (1). This is very good. If your are training hard, but don’t FEEL like you are training hard, this in itself can benefit performance. Other effects of PS include improved ability to concentrate, improvements in short term memory, and improved scores in neuropsychologiocal tests (5,6,7). Most of these studies (if not all) were done on elderly people so the results here may not apply to younger people. Tests examining brain activity in younger adults found increases in EEG readings after PS supplementation (8). Another point is that almost all of these studies used BCPS not SLPS. It appears at this point that the two function similarly so this is not a concern at this point in time.
Cautions
Since most of the early research on PS was done using bovine cortex derived PS, one would ask why switch over to soy lecithin derived PS? There was some concern that viral particles (i.e. mad cow disease) may be transferred from BCPS to the subjects. This has never occurred and was merely an overcautious concern, after all if you are experimenting with people you want to error on the side that does them the least amount of harm. So while this has never happened, it still is a theoretical concern. Fortunately for most of us, the only PS available is the SLPS and viral particles are not an issue with this version of PS. Another concern is that the long-term uses of PS have not been studied. Lower cortisol levels may be good acutely, but what if this develops into an inability to respond to stress? There is no real evidence one way or another but let me offer this insight. After swallowing a couple of capsules of PS, it crosses the GI tract and enters your blood and gets incorporated into your cells. It is placed on an inner portion of the cell membrane and helps to maintain membrane fluidity (9). This portion of the cell is very dynamic and is subject to change based upon a person’s diet. I don’t see long term negative effects with PS via this mechanism. Now as far as PS working as a neurotransmitter and affecting the body, once you go off of it, the body should revert back to its previous normal state, so again I don’t see long term complications associated with its use.
Since most of you will take PS in an attempt to lower your cortisol levels, consider these other facts. First cortisol is sensitive to many things. Lack of sleep, excess protein, stress (any kind), and light all affect cortisol levels in one way or another. To lower cortisol levels naturally get plenty of sleep, don’t get so worked up over things, spend time doing things that relax you, keep dietary CHO higher than protein intake for all meals and most importantly avoid overtraining. The single best method I know of is to keep a training journal and track your progress. If things are not improving you may be doing something wrong.
Summary
OK here’s the final word on PS. I think it can help improve training. It should allow you too handle higher workloads. By handling higher workloads you get a better training effect. This means more muscle size and strength down the road (assuming diet and recovery are sufficient). The dosage to take appears to be 800 mg per day as used in previous studies (they tell 400 mg in the morning and 400 mg at night). Taking more can be more beneficial but you shouldn’t have to. If your cortisol levels get too low then your joints will start to ache and you’ll want to take some type of anti-inflammatory. I don’t feel that the cortisol levels need to be that low (experience joint pain) in order to boost muscle growth. If your cortisol levels are lowered just shy of experiencing any joint pain, and you are taking a prohormone, you should get a nice increase in the testosterone:cortisol ratio and avoid any joint pains. That is why you should stick to the 800 mg/d. Yes I know some may need more, but the only way we can know for sure how much you need is to take some blood samples around your workouts. This is most likely not going to happen, so that is why sticking with what has been shown to work is the safest bet.
References
1) Fahey, TD and M Pearl. Hormonal effects of phosphatidylserine during 2 weeks of intense weight training. Medicine and Science in Sports and Exercise. 1998; 30(5 Supplement):S35 (abstract #201).
2) Griffin, JE and SR Ojeda. Textbook of Endocrine Physiology. 3rd ed. Oxford, NY: Oxford University Press, Inc., 1996.
3) Monteleone, P, L Beinant, C Tanzilo, et al. Effects of phosphatidylserine on the neuroendocrine response to physical stress in humans. Neuroendocrinology. 1990; 52:243-248.
4) Monteleone, P, L Beinant, et al. Blunting by chronic phosphatidylserine administration of stress-induced activation of the hypothalamo-pituitary-adrenal axis in healthy men. European Journal of Clinical Pharmacology. 1992; 41:385-388.
5) Urhausen, A, H Gabriel, and W Kindermann. Blood hormones as markers of training stress and overtraining. Sports Medicine. 1995; 20(4):251-276.
6) Crook, T, J Tinklenberg, J Yesavage, et al. Effects of phosphatidylserine in age-associated memory impairment. Neurology. 1991; 41(5):644-649.
7) Cenachi, T, T Bertoldin, C Farini, et al. Cognitive decline in the elderly: a double-blind, placebo controlled multicenter study on the efficacy of phosphatidylserine administration. Aging Clin. Exp Research. 1993; 5(2):122-23.
8) Delwaide, PJ, AM Gyselynck-Mambourg, A Hurlet, and M Ylieff. Double-blind randomized controlled study of phosphatidylseine in senile demented patients. Acta Neurologica Scandinavica. 1990; 81(3):265-270.
9) Rosadini, G, WG Sannita, F Nobili, and T Cenachi. Phosphatidylserine: Quantitative EEG effects in healthy volunteers. Pharmacoelectroencephalography. 1990; 91:42-48.
10) Bruni, A and G Toffano. Lysophosphatidylserine, a short-lived intermediate with plasma membrane regulatory properties. Pharmacological Research Communications. 1982; 14(6):469-484.
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