Phosphatidylserine Helps You Keep Your Cool

Phosphatidylserine for Mental Health

Phosphatidylserine Helps You
Keep Your Cool

Study demonstrates effect of brain lipids in alleviating
mental and emotional stress
By Dr. Edward R. Rosick

uick—name one activity that most adults have experienced and almost universally despise. Paying their taxes? No, although with April 15 looming, that’s a good guess. The answer we’re looking for is a job interview. Whether it’s for your first job out of college or for an executive position that you’ve labored for years to secure, the dreaded job interview is something that can make even the coolest of people melt down.

Just thinking about this ordeal while driving to the interview, wondering if you’re dressed correctly and trying to guess what type of questions you’ll get, can tie your stomach in knots. Then, when you’re actually sitting across from your potential boss, trying to act composed while sweat puddles are forming and you’re struggling to remember your name, stress-induced biochemical reactions are wreaking havoc on your innards.

What Is Stress?

We all know what that kind of stress feels like when we’re in its clammy grip, but scientifically speaking, just what is stress? Stress is a mentally or emotionally disruptive condition brought about by external influences—usually (but not necessarily) adverse ones—that are capable of affecting not only our state of mind but also our physical health. Typical symptoms include increased heart rate, a rise in blood pressure, muscular tension, and irritability or depression. These result from a host of physiological changes that collectively constitute the stress syndrome.

Implicit in that description is that our state of mind affects our physical health—“mind over matter”—a concept whose scientific validity was established a century ago. Researchers who specialize in the study of stress and its effects on our bodies and minds generally divide it into three broad categories:

  • Eustress is positive and healthful—it’s the kind of good stress we feel when we experience a situation that is inspiring or motivating, such as the excitement of a political rally for a cause we believe in. Eustress is characterized by the release of “feel-good” hormones, such as endorphins.
  • Neustress refers to the neutral feelings arising from input that may be important but that has no significant impact on us—for example, hearing the news of a typhoon in the Pacific Ocean when we’re living in Iowa.
  • Distress is what we usually think of when we hear the term stress. It’s characterized by the release of potentially harmful hormones, such as cortisol and epinephrine (adrenaline), and it comes in two varieties. Acute stress arises quickly but lasts only briefly, then dissipates quickly—the job interview, for example. Chronic stress, by contrast, may build slowly and may last for a long time, perhaps indefinitely—the job itself, for example, which you may come to wish you had never gotten.

Can Stress Harm Your Breasts?

Chronic stress contributes to the development of various diseases, including such major ones as heart disease, cancer, and depression. For example, a recent study examined the effects of stressful past events and job-related stress on the development of breast cancer in women.1 The researchers examined the medical records and emotional histories of 257 patients who had breast cancer between 1993 and 1998, and of 565 controls who were cancer-free. After adjusting for age and other potentially confounding variables, they found that women who had significant life stressors, as well as high levels of stress at work, had a 3.7 times higher risk for breast cancer than women who did not experience such stress.

Clearly, we need to know what we can do to help prevent stress from ruining our life, or even ending it. Some people turn to alcohol or other drugs for relief and solace, but the truth is … well, we all know what the truth is on that score. Two approaches that are far healthier and more effective are exercise and meditation. Although they could not be more different outwardly—they’re diametric opposites, after all—they have one important thing in common: they both induce the release of beneficial hormones that reduce stress. They promote not only a sense of well-being, they promote well-being, period.

Chocolate or Phosphatidylserine? Choices …

If we can combat stress from within, can we also combat it from without, through nutrition? Of course! Although it would be fun to write an article extolling the stress-reducing virtues of chocolate (which are due in part to its phenylethylamine content), we are more concerned here with nutritional supplements that can help lower our stress levels. One such supplement is phosphatidylserine (foss-fah-tide-il-seer’een). What this compound is and why it’s important are outlined in the sidebar “A Phospho-Primer.”

A Phospho-Primer

Your brain cells are rich in fatty compounds called phospholipids, which make up the cell walls of all of its neurons (cell walls are also called cell membranes). These compounds are so important that it’s worth learning a little bit about them, so let’s put those phospholipid-rich neurons to work for a minute, shall we?

You’ve heard the term triglyceride, which is just the technical term for a fat molecule. A triglyceride (fat) consists of three fatty acids (organic acids having long hydrocarbon chains, such as oleic acid or the omega-3s) attached to one molecule of glycerol (which is an alcohol), like three ropes hanging from a bar. Now imagine that in place of one of those fatty acids, there’s an inorganic phosphate group (which is acidic) instead. Presto, you’ve got a molecule called phosphatidic acid, which occurs in very small amounts in cell membranes. It’s the simplest member of a group of compounds called phosphoglycerides, and other members of that group occur in large amounts in cell membranes.

The other phosphoglycerides are made by adding an alcohol to the other side of that phosphate group in phosphatidic acid. When this is done, the resulting molecule is called phosphatidylsomething, the “something” being the name of that alcohol. If the alcohol is serine, e.g., you’ve got phosphatidylserine.* Similarly, the alcohols choline, ethanolamine, and inositol produce phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol, respectively. Together with phosphatidylserine, these are the principal components of cell membranes. All are white, waxy solids in their pure state.

*Wait a minute—isn’t serine an amino acid? Then how can it be an alcohol, which is sort of the opposite of an acid? Well, it’s both an acid and an alcohol (organic chemistry can be tricky).

In summary: to get a phosphatidylsomething, you start with a triglyceride, remove one fatty acid (but keep the other two), replace it with a phosphate group, and then add an alcohol to the phosphate group. These phosphatidylsomethings are all phosphoglycerides, and all phosphoglycerides belong to the larger class of compounds called phospholipids.

Wasn’t that easy? (There will be a quiz.)

Owing to its memory-enhancing properties, phosphatidylserine has long been used for the treatment of age-related memory loss, Alzheimer’s disease, and other forms of dementia. By helping maintain the structural integrity and plasticity of neuronal cell membranes, phosphatidylserine enhances the ability of neurons to fulfill their signal-transmission functions. It’s very safe to use, and there are no known adverse interactions with any other substances, natural or synthetic.

Phosphatidylserine Is Tested for Stress Reduction

A recent study by German and Israeli researchers found that a phosphatidylserine-containing supplement provides some protection against mental and emotional stress, which suggests a potential for the treatment of stress-related disorders.2 The supplement was a commercial formulation called PAS—a mixture of phosphatidylserine (PS), phosphatidic acid (PA), and several other phosphoglycerides (better read that sidebar!).3 The researchers had noted two prior studies, one showing a beneficial effect of 300 mg/day of a PS/PA mixture on memory and mood in elderly subjects, and the other showing a positive effect of 300 mg/day of PS alone on perceived stress during a stressful mental arithmetic task.

For their randomized, double-blind, placebo-controlled study on 80 individuals (40 men and 40 women, aged 20–45), the researchers in the current study used 100-mg capsules of PAS in three different dosages. According to their description of it, each “100-mg” capsule of PAS actually contained 500 mg of ingredients: 100 mg of PS, 125 mg of PA, 270 mg of “other inert phospholipids,” and 5 mg of silicon dioxide (for its anticaking effect). The three dosages used were: 400 mg (meaning 400 mg of PS plus 500 mg of PA and 1080 mg of other inert phospholipids); 600 mg (600 mg of PS, etc.); and 800 mg (800 mg of PS, etc.). These were given daily for 3 weeks.

The “inert phospholipids” were described as PC, PI, and PE (which stand for phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine, respectively), plus something called “Lyso Phospholipids,” which is apparently a trade name. What is curious about this description is that PC, PI, and PE are not inert phospholipids, but biologically active ones. Nonetheless, the authors must have had reason to believe (as implied by the title of their paper) that the efficacy of this formulation would be due primarily to PA and PS (It must be noted that their study was initiated and financed by the Israeli manufacturer of PAS.)

Phosphatidylserine Helps Mitigate a Sweaty Ordeal

To give their 80 volunteers a hefty dose of psychological stress, the researchers used a standardized protocol called the Trier Social Stress Test (named for the German city of Trier, where this study was conducted). The 15-minute TSST, which they described as leading to “a moderate increase in fear,” entails a mock job interview (including the requirement of giving a 5-minute speech, as if applying for a job) followed by a 5-minute-long mental arithmetic challenge—all done before a two-person committee of trained behavioral observers. (It would probably be more fun to poke yourself in the eye with a sharp stick!)

When all the sweat had been mopped up, the results of this study showed that, as expected, the placebo group (controls) experienced marked symptoms of stress from the TSST, as shown by their heart rate, their elevated blood and saliva levels of stress hormones, and their responses to questionnaires regarding anxiety and mood. Compared with the controls, the volunteers who received 400 mg/day of PAS showed a significant reduction in stress hormones (but not in heart rate or in total scores for anxiety and mood). Curiously, the effects of the 600-mg and 800-mg dosages were weaker and did not reach the level of statistical significance; for all practical purposes, they had no effect. This serves as a good reminder of the fact that more is not always better, or even as good.

Some Unanswered Questions

The authors noted that the results may have been gender-dependent to some degree, since the women in the study weighed less and therefore received more PAS per kilogram of body weight than did the men. It was not possible to quantify any such differences, however, owing to statistical limitations arising from the small group sizes. (Regarding gender differences, see the Newsflash sidebar.)

Newsflash: Men and Women Are Different!

In today’s politically correct social climate, the suggestion that there are innate differences between men and women is often derided as “ignorant sexism.” Common knowledge and common sense tell us, however, that men and women are fundamentally different in many ways—one of which is how they react to stress. When suffering from stress, women tend to seek comfort and support by talking it out with family and friends. Men, on the other hand, tend to internalize their stress, allowing it to fester and gnaw at their vitals. By responding in such different ways, men and women show markedly different physiological responses to stress, and men usually suffer greater harm from it—but not always, as the following example shows.

A recently published epidemiological study examined the effects of stress brought about by loneliness in middle-aged men and women.1 The researchers examined 240 working men and women, aged 47–59, and detailed the ways in which stress affected various physiological parameters, including cardiovascular responses. They were able to show that diastolic blood pressure reactions to acute mental stress were positively correlated with loneliness in women, but not in men.

This study and others of a similar kind have provided scientific evidence of what people have always known instinctively—that chronic stress is harmful to our health.

  1. Steptoe A, Owen N, Kunz-Ebrecht SR, Brydon L. Loneliness and neuroendocrine, cardiovascular, and inflammatory stress responses in middle-aged men and women. Psychoneurol 2004;29:593-611.

A more serious flaw in this study was the impossibility of assessing the relative contributions of the various ingredients in PAS, although it was clearly assumed that phosphatidic acid and phosphatidylserine (constituting 25% and 20% by weight, respectively, of the product) played a significant role. As for the supposedly inert phospholipids (54% by weight), one is left wondering why they were included and what their effect actually was.

Remember to Take Phosphatidylserine

As mentioned earlier, phosphatidylserine has shown efficacy in treating memory problems. A recent review article examined the evidence for the use of PS in combating age-related memory decline.4 In placebo-controlled studies with older adults having minimal to moderate cognitive impairment, the results with PS were encouraging. At a dose of 300 mg/day, e.g., PS consistently and significantly improved total recall compared with placebo. And in adults aged 50–75 with no dementia or age-related memory loss, PS again increased memory retention.

Remembering important things (such as your name during a job interview) is very … uh … now I’ve forgotten how this sentence was supposed to end. How embarrassing! I’m feeling stressed. Maybe I should go get some phosphatidylserine …


  1. Kruk J, Aboul-Enein HY. Psychological stress and the risk of breast cancer: a case-control study. Cancer Detec Prev 2004;28(6):399-408.
  2. Hellhammer J, Fries E, Buss C, Engert V, Tuch A, Rutenberg D, Hellhammer D. Effects of soy lecithin phosphatidic acid and phosphatidylserine complex (PAS) on the endocrine and psychological responses to mental stress. Stress 2004;7(2):119-26.
  3. Ruenberg D. Anti-depressant, stress suppressor, and mood improver. U.S. Patent No. 6,410,522, issued June 25, 2002.
  4. McDaniel MA, Maier SF, Einstein GO. Brain-specific nutrients: a memory cure? Nutrition 2003;19:957-75.

Dr. Rosick is an attending physician and clinical assistant professor of medicine at Pennsylvania State University, where he specializes in preventive and alternative medicine. He also holds a master’s degree in healthcare administration.

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