Phospholipid supplements and their health benefits by Ray Sahelian, M.D.
January 20 2016

Phospholipids are essential molecules that are found inl cellular membranes. Two important phospholipids are phosphatidylcholine and phosphatidylserine. A cell in the human body cannot function normally without these two crucial phospholipds. As the name implies, phospholipids are made of the combination of lipids (fats) and the mineral phosphorus.

Phospholipids for brain health
Like omega-3 fatty acids, phospholipids are important for optimal brain health. Phospholipids are found in high concentrations in the lining of practically every cell of the body, including brain cells. They help brain cells communicate and influence how well receptors function. Although present in many foods, phospholipids are found in higher concentrations in soy, eggs and the brain tissue of animals. There may actually be a biochemical rational for the folk wisdom that says eating brain makes one smarter.

Phospholipid supplements
The two most common phospholipid supplements sold over the counter are phosphatidylcholine (PC) and phosphatidylserine (PS). Phosphatidylcholine is also known as lecithin. This page explains the role and function of phospholipids, their clinical effects, and practical recommendations for or against supplementation.

In addition to these phospholipids, I will also discuss choline, a nutrient that helps form phosphatidylcholine. Choline is the precursor to acetylcholine, the brain chemical involved with memory. Choline has been sold over the counter for many years. A new and more activated form of choline, called CDP-choline, became available in the US in 1998.

MIND POWER Rx is a cognitive formula with phospholipid precursors. It combines a delicate balance of brain circulation agents and neurotransmitter precursors with powerful natural brain chemicals that support healthy:

The herbs include: Ashwagandha, Bacopa, Fo-Ti, Ginkgo biloba, Ginseng, Mucuna pruriens, and Reishi. The nutrients and vitamins are Acetyl-l-carnitine, Carnitine, Carnosine, Choline, DMAE, Inositol, Methylcobalamin, Pantothenic acid, Trimethylglycine, Tyrosine, and Vinpocetine.

What benefits do choline and phospholipids Provide?
Individuals who don’t have a good dietary intake of phospholipids may find that taking these nutrients leads to an improvement in learning and memory. Most young and healthy people who take PS or PC are not likely to notice any significant changes, although supplements could help some seniors. The effects from choline, and its cousin CDP-choline, are more noticeable.

Which Conditions Can Phospholipids Benefit?
The clinical application of these nutrients has not yet been fully evaluated, but scientists have studied their role in age related cognitive decline (ARCD), Alzheimer’s disease, and Parkinson’s disease. No firm conclusions are yet available as to whether PS and PC help these conditions. Choline and CDP-choline could potentially be beneficial in ARCD and Alzheimer’s disease.

Healthy cell membranes
A lining called the cell membrane surrounds each brain cell. Without a healthy cell membrane, we cannot have optimum memory and mental function. Phospholipids play several roles in the brain. They not only determine which minerals, nutrients, and drugs go in and out of the cell, but also influence communication between brain cells by influencing the shape of receptors and promoting the growth of dendrites. Since phospholipids help form the cell membrane of the trillions of cells in the body, it makes sense that they would have an influence on not just the brain, but on a number of organs and tissues, including the heart, blood cells and the immune system. As we age, there’s a decline in the amount of phospholipids making up cell membranes (Soderberg 1991).

PLoS One. 2012. Fish oil supplementation alters the plasma lipidomic profile and increases long-chain PUFAs of phospholipids and triglycerides in healthy subjects. In healthy subjects, fish oil supplementation alters lipid metabolism and increases the proportion of phospholipids and triglycerides containing long-chain polyunsaturated fatty acids.

Phospholipids Made Simple
Phospholipids are compounds made of two fatty acids attached to glycerol, the mineral phosphorus, and an amine. An amine is a molecule that has nitrogen attached to a few carbon atoms. The two most common fatty acids attached to phospholipids in the brain are DHA and arachidonic acid. You may recall from chapter 7 that DHA is found in fish oils. Phosphatidylcholine (PC) is the most abundant phospholipid in brain cell membranes comprising about 30 percent of the total phospholipid content while phosphatidylserine (PS) makes up less than 10 percent. The fatty acid content of brain phospholipids can be altered by the composition of the diet, particularly just before and after birth. The phospholipid composition of the brain can be manipulated even in adults. Animal studies have indicated that omega-3 fatty acids added to the diet of rats are able to travel to the brain cell membranes and become part of the phospholipids (Jumpsen 1997). If one’s diet includes seafood, then there will be an adequate amount of DHA present in the phospholipids forming the cell membrane of neurons. The fatty acid composition of phospholipids can deteriorate with aging and disease. As we age, many of the long-chained polyunsaturated fatty acids, such as DHA, can become shortened and more saturated. This can interfere with the optimal functioning of neurons.

Nutr Hosp. 2014. Phospholipids: properties and health effects. Phospholipids are amphipathic lipids, which are found in all the cell membranes, organized as a lipid bilayer. They belong to the glycerol-derived lipids, showing a similar structure as triglycerides. The current interest of them comes from its effectiveness to incorporate different fatty acids in the cell membrane, as they exhibit better absorption and utilization than triglycerides. In this paper, the bibliographical data published about the benefits of the phospholipids in inflammatory processes, cancer, cardiovascular diseases, neurological disorders, liver disease and as an antioxidants transporter is reviewed.

The Making of Phospholipids
In order to better understand how the nutrients in this chapter work, it helps to know how they are related to each other. As you can see from figure 8.1, PS can be converted into PC. Choline converts into CDP-choline and then PC. All of the nutrients listed in this figure, except for acetylcholine, are available over the counter as supplements. Acetylcholine is a brain chemical, among various other functions, involved in memory and learning.

Relation of Choline to Acetylcholine and Phospholipids
Having presented the overview, let’s now discuss specific nutrients and the research evaluating their role in the therapy of cognitive disorders.

Choline helps form phosphatidylcholine, the primary phospholipid of cell membranes. Choline is also the precursor to acetylcholine, one of the important brain chemicals involved in memory. This nutrient, usually as part of phosphatidylcholine, is widely available in a number of foods, particularly eggs, fish, legumes, nuts, and meats and vegetables, as well as in human breast milk. Dietary intake of choline ranges from 300 to 900 mg a day. Most individuals who have a normal diet are not deficient in choline. The importance of choline was emphasized in 1998 when the National Academy of Sciences classified it as an essential nutrient. In the past, it was thought that the human body made adequate amounts when needed. However, a study by Dr. Steven Zeisel, from the Department of Nutrition at the University of North Carolina at Chapel Hill, demonstrated that volunteers on a choline deficient diet were not able to produce enough of this nutrient (Zeisel, 1991). According to the results of several studies in rats, providing choline during pregnancy enhances memory and learning capacity in the fetus (Williams 1998). Dr. Christina Williams, a behavioral neuroscientist at Duke University in Durham, North Carolina, says her study findings demonstrate, "That supplementation with choline during the last third of pregnancy has fairly dramatic and long-lasting effects on the memory of offspring." Several studies have been done administering choline to humans in order to evaluate memory function. The results have been mixed with some showing positive results (Sitaran 1978) while others indicating no improvement (Mohs 1980). Choline has also been tested in bipolar disorder, also known as manic-depression. When six patients already on lithium were given choline bitartrate, five of them had a substantial reduction in manic symptoms (Stoll 1996). A 1997 study published in Advances in Pediatrics by Dr. Zeisel showed that choline reserves are depleted during pregnancy and lactation (Zeisel 1997). This depletion may affect normal brain development and memory in the offspring. The National Academy of Sciences suggests that pregnant women consume at least 450 milligrams of choline per day.

CDP-Choline
Cytidine 5-diphosphocholine is also known as citicoline. This nutrient is approved in Europe and Japan for use in stroke, Parkinson’s disease and other neurological disorders (Secades, 1995). In a way, you could consider CDP-choline as more potent form of choline. Studies show that CDP-choline helps make phosphatidylcholine (PC) in human brain cell membranes in older individuals (Babb 1996); may increase acetylcholine synthesis; improves mental performance in patients with Alzheimer's disease when given at a daily dose of 1000 mg per day (Cacabelos 1996); and even improves memory in elderly patients with memory deficits (Alvarez 1997). A Belgian study has shown that CDP-choline administration to dogs improves their ability to learn and remember (Bruhwyler 1998). Dr. Vittorio Porciatti at the Institute of Neurophysiology in Pisa, Italy, tells me, “CDP-choline is commercially produced in Europe under several product names. Neurologists have found this nutrient useful in Parkinson’s disease, brain trauma, and aging in general. It may surprise you that I mention Parkinson’s disease. In addition to the understandable action on cell membranes, we have been somehow surprised that CDP-choline has dopamine-like effects. Interestingly, dopaminergic-like activity seems to be long lasting, possibly due to stabilization of the effects at membrane level. We have found no significant side effects with CDP-choline even for long therapy cycles. In one study we gave a dosage of 1 gram a day for fifteen days to young individuals. They reported improvement in visual clarity.” (Porciatti 1998)

Phosphatidylcholine (Lecithin)
Lecithin is known as phosphatidylcholine (PC), although it is also a term loosely applied to describe a combination of PC with other phospholipids. Most people normally ingest 3 to 6 grams of lecithin a day through eggs, soy, and meats. Vegetables, fruits and grains contain very little lecithin. PC is the most abundant phospholipid component in all cells. PC levels in brain cell membranes decline with age. Several studies have been done with PC to investigate its effects on memory. The results of the studies have not been consistent. Some have shown positive responses (Sorgatz 1987, Ladd, 1993), while others showed no difference in memory or learning after lecithin administration (Gillin 1980). Lecithin has even been evaluated in Parkinson’s disease (Tweedy 1982). In this nine-week long double-blind study, sixteen elderly patients took a daily dose of approximately 32 grams of a commercial lecithin preparation. Marked clinical improvement was not observed, but there was a slight improvement in memory, cognition, and motility.

Phosphatidylserine (PS)
Although lecithin (PC) has been available as a supplement for many decades, PS became available to the North American market in the mid 1990s. In the past, PS was obtained from the brains of cows. In fact, if you read some of the research studies published on PS, it will identify this nutrient as BC-PS. The BC stands for bovine cortex, or cow brain. The reason BC-PS is not sold is because of the fear of viruses or infectious agents being inadvertently introduced in the PS product when extracted from the brains of cows. The PS currently available over the counter is derived from soy. Several studies have evaluated the role of oral BC-PS administration in both animals and humans. In general, the results have shown positive benefits. However, we need to keep a very important point in mind. The studies with PS have used bovine cortex as the source. Can we assume that the results with soy-derived PS would be similar? Each PS molecule contains two fatty acids. The fatty acids in PS derived from soy are mostly 16 and 18 carbon molecules such as palmitic, oleic, linoleic and linolenic. These are small chain fatty acids and have fewer double bonds than the fatty acids in PS derived from bovine brains, such as arachidonic acid and DHA, which are polyunsaturated and have longer chains of 20 and 22 carbons. Human studies with soy-derived PS have not been published in reliable, peer-reviewed journals. However, there have been a number of studies evaluating the role of BC-PS in cognitive function particularly in age associated memory impairment and Alzheimer’s disease. Most of these studies have indicated that BC-PS improves memory and cognition in those with age related cognitive decline (Crook 1991, Cenacchi 1993), and helps improve memory and recall in patients with Alzheimer’s disease (Engel 1992, Crook 1992).

In food
Almost the all milk fat is closed inside fat globules possessing envelope of phospholipids, glycosphingolipids, cholesterols and proteins. Phospholipids of milk are composed of phosphatidylcholine (lecithin), phosphatidylethanolamine (kefalin), sphingomyelin, also phosphatidylinositol, phosphatidylserine and lizophosphatidylcholine (lizolecithin) and make 30% of the milk fat globule membrane. Phospholipids possess pro-health properties. They act neuroprotectively, regulate brain activity, improve memory and resistance to stress, reduce depression risk.

Food Chem. 2013. Phospholipids in rice: significance in grain quality and health benefits: a review. Phospholipids (PLs) are a major class of lipid in rice grain. Although PLs are only a minor nutrient compared to starch and protein, they may have both nutritional and functional significance. We have systemically reviewed the literature on the class, distribution and variation of PLs in rice, their relation to rice end-use quality and human health, as well as available methods for analytical profiling. Phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and their lyso forms are the major PLs in rice.

Alzheimer's disease
Proc Natl Acad Sci U S A. 2015. Phospholipid dysregulation contributes to ApoE4-associated cognitive deficits in Alzheimer's disease pathogenesis. The apolipoprotein E4 (ApoE4) allele is the strongest genetic risk factor for developing sporadic Alzheimer's disease (AD). However, the mechanisms underlying the pathogenic nature of ApoE4 are not well understood. In this study, we have found that ApoE proteins are critical determinants of brain phospholipid homeostasis and that the ApoE4 isoform is dysfunctional in this process. We have found that the levels of phosphoinositol biphosphate (PIP2) are reduced in postmortem human brain tissues of ApoE4 carriers, in the brains of ApoE4 knock-in (KI) mice, and in primary neurons expressing ApoE4 alleles compared with those levels in ApoE3 counterparts. Data suggest a loss of function of ApoE4 genotype. Together, our data uncover a previously unidentified mechanism that links ApoE4-induced phospholipid changes to the pathogenic nature of ApoE4 in AD.

Questions
Q. Is alpha gpc a phospholipid?
   A. No. Alpha GPC (L-alphaglycerylphosphosphorylcholine) is a phospholipid metabolite found concentrated in neuronal membranes.

Q. I have heard that fish eggs, such as caviar, are a good source of phospholipids.
   A. Yes, fish eggs are a good source. See salmon roe for more info.

Q. Ovosan is a Czech product that, according the their website, "containing biologically active substances that are characterised by the ability to help effectively in the treatment and prevention of tumour diseases." An active substance is ether phospholipid PNAE (plasmanyl-N-acyl-ethanolamine).
   A. We could not find any published research with Ovosan.

What is ehtanolamine, I see it mentioned in some lecithin products.
   Ethanolamine is a common head group for phospholipids which are found in biological membranes.

Do you consider lecithin and phospholipids to be cancerous / carcinogens?
    I don't, they are found normally in many foods.