© Whole Foods Magazine
Phosphatidylserine (PS) 101
An interview with Parris M. Kidd, PhD
By Richard A. Passwater, Ph.D.
Much of what I have learned through the years about phosphatidylserine (PS) has come through the writings of Parris Kidd, Ph.D. Perhaps, that is true for you as well. With the aging of the population, PS is becoming more important to more people. So, I feel it is a good time to chat with Dr. Kidd about PS basics and to try to clarify a few over-simplifications that may exist.
PS is a dietary supplement that reverses memory loss and cognitive decline, enhances concentration and word skills—particularly in people over 50. PS is an important supplement for the young as well, as it protects against mental and physical stress, improves performance and reduces overtraining effects.
The U.S. Food and Drug Administration (FDA) permits the following health claims for PS:
* PS may reduce the risk of cognitive dysfunction in the elderly.
* PS may reduce the risk of dementia in the elderly.
I don’t believe that even pharmaceuticals have been shown to help cognitive function as well as PS has been shown to do in clinical tests such as those we discussed in our chat with Dr. Thomas Crook. (August 2005).
Passwater: Dr. Kidd, you have been the leading authority on the nutritional applications of PS since you helped bring it to North America in 1994. Nearly everyone who has studied PS begins by reading your articles and books. What drew your interest to PS?
Kidd: PS is a key building block for cell membranes, the dynamic structures that make cells alive. I was trained in cell biology at the University of California at Berkeley, and while there I did my Ph.D. research on cell membranes. My passion for cell membranes continues to this day. Interestingly, nutrients that feed cell membranes turn out to have highly potent clinical applications and make great dietary supplements.
Passwater: Many know that PS helps restore memory. Few understand how. Let’s begin with the basics. The PS phospholipids are a subfamily of compounds within the family of compounds called phospholipids. What are phospholipids?
Kidd: Phospholipids are literally lipids that contain phosphorus. They are different from fats, which don’t contain phosphorus. Whenever I hear of PS being called a fat I cringe. The phospholipids are a unique nutrient category.
The phospholipid molecule (PL, for short) is a complicated molecule with a head, a middle piece, and two tails (rarely, one tail only). The middle piece is originally a 3-carbon glycerol molecule. Carbon 3 carries a head group, which can be made from choline, ethanolamine or inositol, or from serine, as in the serine phosphoglycerides better known as PhosphatidylSerine, or PS for short. Carbons 1 and 2 almost always carry 2 fatty acids attached to them. These fatty acids can be saturated, monounsaturated, omega-6, or omega-3.
Figure 1 shows the general chemical structure of a PL. The total PL molecule is customized by nature to make cell membranes. PS and other PLs self-assemble into the membrane configuration. I talk about membranes and their innumerable life functions in my book on PS that is now in press.
Figure 2 shows how PLs arrange themselves to allow membrane formation that is necessary for life. The PS molecular layout (left) and its placement in the outer cell membrane (right). PS is preferentially located in the inner membrane half, often enwrapping key membrane proteins. This illustration is copyrighted by Kidd PM, 1998, and appears in my forthcoming book, PS, Nature’s Brain Booster.
Passwater: I know that you are not pleased at the manner in which many people in the industry tend to refer to phospholipids as “good fats.” Perhaps they see everything in nutrition as fats, proteins, carbohydrates, vitamins and minerals. Please point out why phospholipids should not be classified as “good fats” and do you have any suggestions to help the non-scientists classify phospholipids?
Kidd: I’m so glad you asked this question. Let me say first off, there are virtually no bad fats in nature. All fats play good roles when the healthy body is allowed to use them as they were meant to be used. The only bad fats are some that are manufactured by humans. Many of these do bad things by interfering with the natural workings of cell membranes. Fats are triglycerides, glycerol combined with fatty acids. Phospholipids are also glycerides, and also contain fatty acids but are more complicated than are fats.
As I pointed out earlier, PLs aren’t fats at all. They are specialized lipids. “Lipid” is a practical, operative chemical term for a molecule that can be dissolved by a solvent that lacks charge. All fats are lipids but many lipids are not fats. All phospholipids are lipids but not all lipids are phospholipids. Cholesterol is not a phospholipid but is also essential for cell membranes (in very small quantities). This is one of many reasons why there is also no bad cholesterol.
Because of all this confusion and overlap of terms, not to mention the complexity of the very word phospholipid, I’m getting into the habit of calling phospholipids by the trademarked term “Vital Lipids.”
Passwater: What do phospholipids do?
Kidd: To answer briefly, I can say that PLs perform many important roles for living things. They make up cell membranes, the dynamic structures used by every cell of all living things to maintain life and carry out specialized functions. The phospholipids are key membrane building blocks. They are as crucial for life as DNA, RNA, and proteins. PLs also are building blocks for the circulating lipoproteins, the small particles that transport nutrients to the tissues and remove excess substances from the tissues for disposal by the liver.
PLs are surface-active agents—they are used to facilitate biological functions at the water-air interfaces in the lungs and intestine. PLs are used by the liver to make bile fluid for the digestion of the lipids in our foods. Some PLs are processed by enzymes to make hormones or nerve transmitters. PS and the other phospholipids are part and parcel of life processes, from life’s very beginnings up to the sophisticated human being.
Passwater: What is important about the molecular structures of phospholipids that allows them to function?
Kidd: This question also invites a long answer. I can immediately think of two key properties of the PL molecule that are most important: one, the molecule is uncharged at one end and charged at the other, which is great for assembling into membranes and other biological structures with almost zero cost of energy. PLs are major building blocks of life. Two, the different head groups have very different three-dimensional and charge arrangements that suit them for specific subdivisions of function within membranes (and elsewhere).
Another important aspect of the PL molecule is that it has molecules within molecules. The head groups can be added and removed and used for important life functions outside of the phospholipid parent molecule. The fatty acid tails are another whole story. They are routinely modified, added, removed, or switched around as the parent PL molecule sits in the membrane. All the biological effects of the omega-3s are accomplished with them integrated into membrane phospholipids. In the brain, the omega-3 DHA as part of PS is a uniquely important molecule for a variety of functions.
Passwater: Let’s start with the basics for our readers. What is PS?
Kidd: Well, our readers will love to read my new book on PS. It’s a PL with a serine head group, found in all cell membranes of all known life forms. It is especially concentrated in the brain. There are many different subtypes of PS molecules in the brain, because the two tail groups can come with different combinations of fatty acids. The most common fatty acids in the brain’s PS are stearate (18:0), oleic (18:1 omega-9), and DHA (22:6 omega-3). Other organs have different fatty acid profiles—the head group and middle piece are the same but the tail groups vary according to the needs of each organ.
Passwater: What does PS do?
Kidd: I wish I really knew for sure. Sometimes I daydream that I’m part of cell membranes just as they are part of me. I’m swimming inside the highly fluid cell membrane, observing all the incredible life events as they happen. I wish I could see the PS molecules as they wind around many of the cell membrane proteins, giving them a micro-environment, a kind of molecular ecology for these proteins to function at their best.
PS helps to optimize a number of membrane proteins that are very important for the nerve cells to generate energy, spark electrical impulses, become activated or deactivated, coordinate signaling within the brain. In the mitochondria that make the energy in all our cells, PS is important for making the energy-producing membranes. And in all our tissues PS is a key player in disposing of dead and dying cells. Immune cells use the state of membrane PS as a kind of marker to flag a cell for recycling.
In the brain, one protein complex—protein kinase C or PKC for short—is tightly linked to memory formation. It’s the only protein known to change as a new memory is being laid down. PS is absolutely essential to the activation and overall functionality of PKC. This alone could account for most of the clinical benefits of PS seen by Dr. Tom Crook and others. But PS is also doing lots of other good things in the brain.
PS with DHA attached is a highly efficient membrane fluidizer. And in nerve cells, as a rule the more fluid the membranes are the better they function. At the whole-body level, there’s highly persuasive evidence that the PS subtype that carries omega-3 DHA has regenerative effects on the brain. There is solid evidence—documented in my book—that by taking PS and DHA we can actually rebuild lost or damaged brain circuits.
Passwater: What is unique about the structure of PS that allows PS to function?
Kidd: The entire molecule as it is—the serine head, the glycerol middle piece, a saturated or monounsaturated fatty acid on tail 1 (most often, though not always), and a polyunsaturated fatty acid on tail 2. A negative charge on the serine head is important for many of its unique membrane functions.
Tail 2 also is crucial to the biological actions of PS. When DHA is in that position the membrane benefits of PS are most potent, and it may well be that PS-DHA has the most intense regenerative effects in our brain cells.
Passwater: So, the negative charge on the serine head of PS is important, though not the whole story. But what’s so unique about PS compared to the other phospholipids in membranes?
Kidd: PS is unique by being PS. Nature has designed each of the phospholipids to do unique things in cell membranes. The other phospholipids are important for their specialized functions, and so is PS. It uniquely occupies a special position on the inside half of the cell membrane, and there it works with a number of membrane proteins that happen to be highly important for brain functions. So important are these PS and protein interactions that the clinical research done on the brain was able to show dramatic benefit from supplementing with PS.
It seems that the availability of PS to membranes limits a number of these important membrane functions, and when someone’s enzyme systems can’t make enough PS they benefit from dietary supplementation. Let’s also remember that PS is used as a starting source to make other important phospholipids, including PE and PC.
Passwater: Does the body make PS?
Kidd: Yes. The body can and does make PS. There are easy ways and hard ways for the human body to make it. Both require specific enzymes. The easy way requires relatively little energy, the hard way requires both lots of energy and lots of nutrient cofactors. Probably most if not all the PS made in the body is by the easy way, headgroup exchange. This involves enzymes making PS from other phospholipids, but sometimes the supplies of these may limit PS production. And the other phospholipids in turn have to be made from scratch, which requires lots of energy and nutrient cofactors.
Also, the healthy brain and body may have to be making a lot of PS because the “draw” on PS in the tissues can be great. A lot of PS is used to produce the phospholipid PE (PhosphatidylEthanolamine), and there’s actually more PE in our cell membranes than there is PS. I suspect that for many people, particularly as they get older, PS is a conditionally essential nutrient—these people are not making sufficient PS and therefore experience better brain performance and quality of life by taking it as a supplement.
Kids with attention and behavior problems stemming from neurologic impairments also seem to benefit from generous amounts of supplemental PS. It may simply be that they need more PS as they attempt to rebuild and redesign their damaged brain circuitry. PS has shown great trophic (regenerative) effects in animal experiments.
Passwater: Does PS production decline with age?
Kidd: Probably, like everything else. But we don’t see this in the PS content of the cell membranes. Human cell membrane PS content doesn’t seem to decline with aging or with disease. But PS is essential to the membrane being a membrane, so that it may be that a lack of PS cuts off membrane production. Period.
It’s likely that the supply of PS limits the amount of new membrane that can be made. PS is so important to membranes that lack of supply would limit the ability of nerve cells to produce new extensions and new connections (synapses).
Some people say that the brain becomes deficient in PS with age; I’ve exhaustively searched the scientific research literature and cannot find any evidence of this. The unit content of PS in cell membranes doesn’t change with age. It may be that for all kinds of reasons having to do with aging, stress, chemical toxicity, or nutrient cofactor deficiencies, an individual comes to make less PS. As her PS production declines, she can no longer replace nerve cell membrane mass and so loses nerve cell circuits faster than she can replace them. At that point, bringing PS in from outside the body could then allow for membrane formation to resume. As a result, new brain circuits then can be formed. Memory and other brain functions are revitalized.
Passwater: You’ve said that for a particular tissue PS content in the cell membrane is characteristic and doesn’t seem to change with age. You point out that the advantage of taking PS supplements would therefore lie in the body being able to make more membranes. Perhaps we can elaborate further on the advantages of making more membranes.
Kidd: This is a deep question, since membranes basically drive life. The scientific libraries have lots of books on membranes, so my answer will be simplistic. Our cells are continually replacing membrane mass that is lost to damage, whether from toxins that come in with the air, water, or food. Also, oxygen free radicals cause ongoing membrane destruction. These are unavoidably generated as we use oxygen to make energy, and as they damage our cells over time are a likely cause of aging and disease. So, ongoing membrane renewal is mandatory for us to function and stay alive. The more PS we have available, the more completely and efficiently we can stay ahead of the biological game of life.
Passwater: Also, from what you have told us, it appears that taking PS supplements wouldn’t affect membrane fluidity or the membrane PS/cholesterol ratio. Am I correct with this conclusion?
Kidd: Yes, you’re correct. Another challenging question. Gosh, Dick, you sure are a tough interviewer. The PS/cholesterol ratio is homeostatically regulated by enzymes in the membranes, more or less independent of dietary inputs.
Taking PS by itself is unlikely to change membrane fluidity. This is because newly absorbed dietary PS has been stripped of its fluidizing fatty acids.
As PS is being absorbed from the intestine, about half of its fatty acid tails are removed. What is lost is up to 100% of its number 2 tail, which is where the DHA and other unsaturated fatty acids usually are carried. So PS by itself won’t substantially affect membrane fluidity. However, if the PS supplement also includes DHA, this would be absorbed separately from PS and become available for wherever the body needs to have it most. Often it finds its way to the brain and then can become attached to PS, where it helps to improve membrane fluidity. Like two passengers taking different roads to arrive at the same destination.
Passwater: It also appears to me (based on the 1995 report of G. H. Lopez et al (Comp. Biochem. Physiol.) that the PS fatty acids can change over time and that fatty acid nutrition may be a way of improving membrane fluidity by incorporating more PUFA such as DHA and other omega-3s into the existing PS already in the cell membrane. Is this a good assumption?
Kidd: Yes. In fact, PS fatty acid tails are continually being shuffled, to suit the changing needs of the cell. This is not a random process, rather it is homeostatically controlled using membrane enzymes because it is crucial to membrane performance and therefore to overall cell survival. The more DHA and EPA in our total diet, the better the prospects for ongoing cell membrane health via good fluidity.
Passwater: Would taking PS supplements with substantial added DHA be a good way of improving PUFA content of membrane PS, via exchanging PUFA from the supplemental PS?
Kidd: Yes, it would. It ensures that DHA is available, to be drawn upon for insertion into PS as the brain needs it.
Passwater: Where do we find PS in the diet?
Kidd: More so from animal foods than from plants. Brain has the most PS, but we don’t eat brain anymore. Eggs have a decent amount, and muscle has some. Plant foods supply very little of it.
Passwater: Do typical diets meet our PS requirements?
Kidd: This is the big question. The typical daily diet supplies very little PS—by my estimates, no more than 75-90 mg per day. By supplementing with three times or greater than the estimated daily dietary intake, clinical researchers have observed clear benefits for memory and learning, for mood, for anxiety, for coping with stress. A number of double-blind trials indicate that PS can benefit people of all ages, from the elderly to college students. Preliminary pilot studies that physicians conducted with my help even suggest that kids may benefit from PS.
Passwater: How much should people take as a dietary supplement?
Kidd: People having trouble with their brains should take 300 mg a day (with meals) until they experience improvement. They should plan on taking this for three weeks to three months; in children the benefits for attention and behavior may take as long as four months to manifest. As a maintenance intake—for mental tune-ups, especially for the person taking lots of nutrients—I’ve suggested 100 mg a day. This really is the minimum, though. Small kids need 200 mg, teenagers generally 300 mg.
Over the past years I’ve come to figure out that people who are well supplied with omega-3 DHA stand to benefit more from PS. The reason for this clinical synergy is the fundamental functional synergy of PS and DHA within our nerve cell membranes. We should all be taking DHA anyway, for our circulatory health, against inflammatory conditions, and for high quality of life. For our brains, PS and DHA are foremost.
Passwater: Is PS being used to treat any clinical disorders?
Kidd: Only for almost everything that can go wrong with the brain. You know, this is why I’m glad I didn’t go into pharmaceuticals. Drugs cannot approach the profound beauty of action of the orthomolecular nutrients, of which PS is one. The great two-time Nobel prizewinner Professor Linus Pauling hit the nail on the head, when he pointed out that substances orthodox to the human body—ortho molecules—make the safest and most efficacious therapeutic agents.
The body has evolved with its orthomolecules as culmination of more than 3 billion years of the existence of life forms. In the case of PS, every biochemical—metabolic—physiologic brain process involves this orthomolecule in one way or another. This is how, so differently from drugs, for people of any age, PS is truly a brain normalizer. PS benefits memory, learning, mood, word recall, comprehension, to a degree that the person notices the improvement. For people who are older, it’s often a brain revitalizer. For the elderly, PS sometimes will rejuvenate the brain, literally. Its benefits for mood and anxiety have been underemphasized in favor of its memory benefits, but its great for all these problems.
One slide I always show in my teaching about PS is that of a woman with Alzheimer’s, whose entire brain turns on like a light after three weeks on 500 mg of PS (Figure 3). This was shown by PET imaging that measures energy generation in the brain. And yes, 500 mg a day can be taken without problem.
The most accomplished integrative practitioners in North America routinely include PS in their protocols for patients with virtually any kind of brain problem. PS is not a panacea for the brain, but any effort to treat declining brain function would be incomplete without including it. For kids, it definitely should be given along with DHA, and I suspect adults also will have better benefits from PS-DHA combinations. Combinations of nutrients are always best, of course, and this is another example where nutraceutical healing diverges from the drug culture.
Passwater: In my preceding interview with memory expert Dr. Thomas Crook, he talked about his work with you on PS as a dietary supplement. How did this come about?
Kidd: The sponsors of my work at that time wanted to be sure that what I was telling them made sense. This is only reasonable; the process is called peer review. Dr. Crook, being the foremost researcher on memory, and having done two landmark clinical trials on PS, was kind enough to do this peer review. We continue to have productive ongoing collaboration in this area.
Passwater: Where is research heading with PS?
Kidd: I would like to see research done that would better define its clinical synergy with DHA. Also, to further explore its benefits for children. Ultimately, it would make my day to find out at the cell level just how PS is able to accomplish the profound revitalizing effects on the brain that it seems to have. I also fully expect that within the next decade PS will be used to crank up stem cells before, during, and after they are implanted into the injured or demented brain.
Passwater: What are your current research interests?
Kidd: Phospholipids. In addition to PS, I am working on GPC (GlyceroPhosphoCholine), a unique water-phase phospholipid that neatly complements the actions of PS. PC (phosphatidylcholine) has been disrespected but is the most common PL in our cell membranes, and I am working on novel preparations of this molecule. I also broadened my interests to include the omega-3 fatty acids, since their actions are exclusively through membrane phospholipids.
With more than 65 double-blind trials on the phospholipids, hundreds of human studies, and thousands of basic science papers, plus the omega-3s being such a hot topic, I have my hands and mind full. I wouldn’t have it any other way.
Passwater: Where can readers find more information on PS (your books, website, etc.)?
Kidd: My book PS, Nature’s Brain Booster should be out very soon. It’s published by Total Health Publications, (www.totalhealthmagazine.com) Besides covering all the health benefits of PS, this book lays out 10 practices for brain health within the context of total health management. I’ve done my best to make it readable and informative for everyone.
My website is www.dockidd.com. It’s loaded with free information. I’ve also written many popular articles on why people should take vitamins, how nutrients protect against toxins and other stressors, and lots of other information for lay people. For doctors and other health professionals (also free for lay people), there are my Alternative Medicine Review publications in downloadable form. Around the brain, I’ve reviewed memory decline, Parkinson’s, multiple sclerosis, bipolar disorder, ADD/ADHD and autism (in two parts). All have integrated protocols for effective efforts at medical management.
For PS, GPC, and other phospholipids I contribute to (www.phospholipidsonline.com). This is also a freely accessed educational website. Interested individuals can reach me through either of those portals.
In closing, I want to thank you and WholeFoods magazine for a highly intelligent and stimulating interview. I respect your universe of contributions to health through nutrition and admire you as a human being. And I thank Science and Ingredients, Inc. and Mr. Peter Rohde for sponsoring my phospholipid work and the new book. Their generous contributions allow me the privilege of studying these fascinating substances and using them to help people.
This has been fun, Dick, for me to talk with a colleague who really is into understanding PS. With all that we’ve talked about today, there’s still a lot about PS that’s not understood, including how it can have such a marked trophic (regenerative or revitalizing) effect on the brain. As a mature life scientist I’ve learned to respect the mysteries of nature and be thankful for what I think I understand, for what I think I can predict. I am grateful that PS is both safe and effective, and its fascinating mysteries I hope to continue to explore.
Passwater: Thank you for all of your research and teachings over the years and for chatting with us about PS.
Figure 1. The general chemical structure of a phospholipid (PL).
Figure 2. The phosphatidylserine (PS) molecular layout (left) and its placement in the outer cell membrane (right). PS is preferentially located in the inner membrane half, often enwrapping key membrane proteins. ©Kidd PM, 1998. From PS, Nature’s Brain Booster, upcoming from Dr. Parris Kidd.
Figure 3. PET scanning measures energy production in the brain. This woman with Alzheimer’s had very poor energy production in her brain (top row of scans) until after receiving PS at 500 mg per day for three weeks (bottom row). Note the scale at right, with yellow and red being the highest energy levels. The three scans on each row are different levels of the same brain. Thus the top three scans are before PS supplementation (almost all blue), the bottom three scans are after 3 weeks on PS supplementation (reds and yellows). From Klinkhammer and colleagues, cited in PS, Nature’s Brain Booster, upcoming from Dr. Parris Kidd.
© 2005 Whole Foods Magazine and Richard A. Passwater, Ph.D.
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