Brain Health Dietary Supplements: This Is Your Brain on Phospholipids

October 9, 2012

Phospholipid brain-health dietary supplements can be the foundation of a healthy mind.

Don’t let age fool you: the brain supplements market is young, but thriving. Look at the numbers. According to market researcher SPINS, combined mass-market and natural channel retail sales grew almost 18% in the past year, spanning everything from acetyl-L-carnitine and Ginkgo biloba to fish oil and omega-3 fatty acid DHA specifically, vitamin B12, DMAE, and vinpocetine. That means that while cognitive health supplement sales a year ago were close to $42 million, today they now stand at close to $50 million.* Clearly, consumers, ingredient developers, and scientists are gravitating to the idea of nutritional ingredients for a healthy mind.

There are many components of brain health. Some cognitive supplements target stress and mood. Others power brain cells with amino acids like acetyl-L-carnitine and glutamine. Botanicals like Gingko biloba and vinpocetine help promote circulation in the brain. Still other interest areas in the cognitive supplements market are addressing oxidation and inflammation.

Obviously, the brain’s structural health is key to such functions as memory and cognition, including mental energy, focus, and concentration. Maintaining structural integrity includes keeping brain cells healthy: ensuring cell walls remain fluid so that they can effectively regulate nutrients coming in and waste going out, and supporting signal-transmitting chemicals in the brain called neurotransmitters.

Lipids are a key component of the body’s cells overall. Phospholipids, a class of lipids, are especially crucial to the health of both cell membranes and neurotransmitters. Brain cell membranes are rich in two phospholipids in particular: phosphatidylserine (PS) and phosphatidylcholine (PC), with PC accounting for a larger percentage. Ensuring a steady supply of PS and PC through diet and supplementation can help in the fight to dissuade age-related cognitive decline and illnesses.


Brain Health: Phosphatidylcholine (PC) & Choline

PC came to the fore in the 1980s as a key brain phospholipid and a crucial component of healthy brain cell membrane. PC supplements on the dietary supplements shelf are often broadly referred to as “lecithin,” because PC is the major phospholipid component of lecithin.

As Kira Schmid, ND, associate director of scientific affairs for dietary supplements brand Life Extension, explains,“Lecithin is a generic term to designate any group of yellow-brownish fatty substances occurring in animal and plant tissues, composed of phosphoric acid, choline, fatty acids, glycerol, glycolipids, triglycerides, and phospholipids (e.g., PC, phosphatidylethanolamine, and phosphatidylinositol).”

Although lecithin products can be formulated to contain higher amounts of PC, many say that in general, lecithin supplements are not very bioavailable sources of PC. And, as Steve Holtby, president and CEO of contract manufacturer Soft Gel Technologies Inc. (Los Angeles), explains, “As a nutritional supplement, PC is hoarded by the liver. As a result, hardly any of it actually makes it to the brain. This is why there are no solid, repeatable clinical studies correlating PC use with cognitive improvement.”

Chase Hagerman, business development and marketing manager for ingredients firm Chemi Nutra (White Bear Lake, MN), adds, “Research has shown that PC is not nearly as effective as a cognition compound as is PS, another phospholipid component found in lecithin but in much smaller amounts. In fact, commercially, PS is produced in a complex processing procedure starting with PC.” (Read the latter half of this article for more on PS.)

Additionally, lecithin supplements are considered poor sources of choline, a nutrient of great interest in the cognitive sector.

What is choline? PC is a key donor of choline, which is often associated with the family of B vitamins. While not a phospholipid in and of itself, choline forms acetylcholine, the brain’s most important neurotransmitter responsible for regulating cognition and memory. (By contrast, PC may not be as effective at converting to acetylcholine after ingestion.) In 1998, the U.S. Institute of Medicine officially recognized choline as an essential nutrient, establishing an Adequate Intake Level of 550 mg/day for men and 425 mg/day for women and an Upper Tolerable Limit of 3500 mg/day.

In the diet, choline is obtained from soybeans, eggs, liver, beef, milk, and cruciferous vegetables. Various sources of choline are also sold in the dietary supplements market, including choline salts such as choline bitartrate and choline chloride, and choline citrate. Some sources may cross the blood-brain barrier better than others.

Of choline chloride and choline bitartrate, Chemi Nutra’s Hagerman states, “Here is where the science comes into play: a number of published research studies conclusively demonstrate that commonly used choline compounds like choline chloride and choline bitartrate do not affect brain function, as they are totally ineffective at crossing the blood-brain barrier.”

By contrast, two other choline donors—alpha-glycerylphosphorylcholine (A-GPC) and citicoline—arepromoted as being more bioavailable sources of choline.


In terms of A-GPC’s choline content and bioavailability, “A-GPC contains approximately 40% choline, on a weight basis, which is very potent,” Hagerman says. “And, more importantly, due to its electrical charge characteristic (polarity) in the tissues, A-GPC releases its ‘choline payload’ very effectively—much more so than PC supplements, which normally comprise between 14–35% PC.” Chemi Nutra supplies its soy-derived AlphaSize A-GPC ingredient.

Ingredients firm American Lecithin Co. (Oxford, CT) also describes A-GPC’s bioavailability, on its website for branded A-GPC ingredient Alcolec GPC. “Because Alcolec GPC lacks the hydrophobic fatty acids typical with PC, its enhanced bioavailability allows it to easily pass through the blood-brain barrier, raising blood and brain choline levels safely and efficiently.”

Hagerman says a number of studies support A-GPC’s bioavailability claims. There are also studies suggesting that A-GPC may even work “more swiftly and more completely” than citicoline, another bioavailable choline source (R Di Perri et al., Journal of International Medical Research, 1991; and L Frattola et al., Current Therapeutic Research, 1991).

A-GPC may also be easier to work with from a formulation standpoint, Hagerman says. By contrast, he says, a concern with PC when used as a dietary supplement ingredient is that high-PC phospholipids can be very gummy and can oxidize easily, creating “off” flavors in finished products and thus making for a short shelf life in finished products.

Ingredients supplier Enzymotec USA Inc. (Morristown, NJ) offers two forms of A-GPC: a soy-derived powder form, Sharp GPC, and a liquid form, Sharp GPC Active. Enzymotec USA’s CEO Elzaphan Hotam adds that this liquid form does not require the addition of any stabilizers, taste modifiers, or flow modifiers.


Cytidine 5-diphosphocholine (also known as citicoline or CDP-choline) is an intermediate compound that occurs when choline converts to PC. Before citicoline reaches the brain, it breaks down into choline and cytidine, which is another important nutrient. Each is transported separately into the blood and then into brain or other tissues. In older subjects especially, higher brain levels of cytidine have been shown to increase the levels of PC incorporated in brain cell membrane, explained SM Babb et al. in the journal Psychopharmacology (1996).

Kyowa Hakko USA (New York City) supplies the patented Cognizin brand of citicoline. The company calls the presence of cytidine in citicoline “the differentiator [that] makes citicoline the more advanced brain ingredient than choline alone.” The company says that Cognizin has been shown to support healthy brain metabolism as well as protect against free radical damage. It has also been shown to increase adenosine-5’-triphosphate (ATP), a key energy source for the brain. “Choline alone does not do this,” the firms says.

Kyowa Hakko USA recently saw the publication of Cognizin’s largest human trial to date, in the journal Food and Nutrition Sciences (June 2012). The 28-day study performed on 60 healthy middle-aged women, at doses of either 250 or 500 mg, showed improved performance with both doses during cognitive function tests. According to the study’s authors, “To our knowledge, this study is the first to examine the effects of low doses of citicoline on cognitive performance in healthy female adults.”