Phospholipids: New uses for an old friend

Running with one of the few FDA-approved health claims and a mass of clinical research, why are phospholipids not a market blockbuster such as DHA? Mark J Tallon, PhD, investigates the latest research and unexploited marketing opportunities

Ask most health-product consumers what fish oils are for, or ask a sports enthusiast what creatine is. Most will be able to provide a credible comment. However, ask the same group what about phosphatidyl-choline (PC) or phosphatidylserine (PS) and you are likely to be met with silence. The easy answer is that most of the public cannot connect with science when delivered in complex language. There are very few products currently on the market leading with a consumer-friendly message to market their products. Additionally, most are multi-ingredient mixes with few carrying the FDA's required 100mg 3x-a-day dose, as with PS.

The effect of these factors makes for a poor sell with little or no emotional connection to the consumer. When fish oils first hit the market, they could connect to an ethos of a 'good for you' food source. As such, their initial pitch to the market was as fish oil and not EPA or DHA derivatives. Eventually, as the market, science and consumer education grew, manufacturers could add new front-of-pack language, like DHA. Even now we see few functional products marketed as docosahexaenoic acid or eicosapentaenoic acid, but rather on their functional influence — healthy brain or IQ, vision, etc.

Despite failures and few, if any, products making it into the functional-foods and beverages category, it is still possible to take these ingredients and make them a success. Recent publications have highlighted new avenues for application as well as new derivatives with the potential of being more efficacious than their predecessors. The following provides a modicum of basic science, and then a brief look at the latest trials on the phospholipid class of ingredients.

The headliners
At present there are three main classes of glycerophospholipids being sold as dietary supplements, despite there being hundreds of phospholipids. These include phosphatidylserine (PS), phosphatidylcholine (PC), and glyceryl-phosphorylcholine (GPC). Most phospholipids are essential building blocks of cell membranes, acting not only as structural molecules but also as dynamic, functionally important components of cells. Here is a brief overview of the most recent research trials on these highly bioactive nutrients.

PS is concentrated in the brain, comprising 15 per cent (30g) of the total phospholipid pool. The average daily intake of PS is currently estimated at 130mg per day for those of us in the West.1 Because of PS location in the internal layer of cell membranes, it can directly interact and modulate the action of receptors, enzymes and ion channels.

Supplementation with PS has been shown to be beneficial in brain function,2 behavioural disorder,3 and stress.4 Some of the most recent research has focused on sports applications and performance.5

In a recent randomised, double-blind, placebo-controlled study, the effect of oral PS supplementation was investigated on golf performance in healthy young golfers.6 Perceived stress, heart rate and the quality of the ball flight was evaluated before (pre-test) and after (post-test) 42 days of 200mg/day PS intake in the form of a nutritional bar. Subjects teed off 20 times, aiming at a green 135 meters from the tee area.

PS supplementation significantly increased the number of good ball flights, whereas placebo intake had no effect. PS supplementation showed a trend toward improving perceived stress levels during teeing off, whereas stress levels remained unchanged in the placebo group. The potential implications are improved golf scores with continued use.

PC supports the regeneration of cell membranes, as well as provides a protective effect to the liver, lungs, GI tract and kidneys.7 Delivered in supplement form PC has been shown to support healthy cholesterol,8 liver9 and brain functions,10 and exercise performance.11 It has been suggested that a large proportion of PC's beneficial effects come from its choline content, which is equal to 15 per cent of the PC molecule.

Heart health has been a major interest in condition-specific supplementation for some time. In a recent trial, researchers studied PC supplementation on risk factors (homocysteine) associated with an increased risk to cardiovascular disease.12 The objective was to investigate whether PC reduces fasting and postmethionine-loading concentrations of plasma tHcy in healthy men with mildly elevated plasma tHcy concentrations.

In a crossover study, 26 men ingested approximately 17.3g/day PC or a placebo oil mixture for two weeks in random order with methionine-loading tests performed on the first and last days of each supplementation period. PC for two weeks decreased mean fasting plasma tHcy by 18 per cent. On the first day of supplementation, a single 10g PC dose reduced the postmethionine-loading increase in tHcy by 15 per cent. PC for two weeks reduced the postmethionine-loading increase in tHcy by 29 per cent, relative to placebo. If high homocysteine concentrations are a significant cause of cardiovascular disease as research suggests, PC intake may reduce cardiovascular disease risk in humans.

GPC is a cognitive enhancer whose mode of action is considered to involve the release of free choline in a similar manner to PC. It has many potential health effects, with those on cognitive function the most widely recognised.13 Although recent trials have focused on vascular dementia and cognitive function,14 some of the most marketable applications were seen back in the 1990s.

It is well known that as we age, growth-hormone (GH) levels fall. In one trial, alpha-GPC was investigated for its potential to modulate GH levels in both young and elderly subjects.15 In order to learn what effect alpha-GPC had on GH secretion, GH-release hormone (GHRH) was given to young and old human volunteers, with or without the addition of alpha-GPC.

GH secretion was greater in the younger subjects than in the older ones, and while both had a greater GH response to the GHRH+a-GPC than to GHRH alone, it was the elderly who showed the greatest GH response to a-GPC. These findings confirm that increased cholinergic tone with a-GPC enhances GH release.

Phosphatidylinositol (PI) is the essential determinant for K+ permeability involved in gastric-proton pumping. Additionally, PI is a component of membrane phospholipids, and functions both as a signalling molecule and a compartment-specific localisation signal in the form of polyphosphoinositides. Although little work has been carried out on this phospholipid, a 2008 trial assessed the effects of PI on nonalcoholic fatty liver disease (NAFLD), a condition closely related to metabolic syndrome.16

NAFLD encompasses the spectrum of liver damage ranging from hepatic steatosis to steatohepatitis, liver fibrosis and cirrhosis, and it is emerging as the most common liver disease worldwide.

The present study examined whether dietary PI protects rats from metabolic syndrome-related NAFLD. For four weeks, rats were fed semisynthetic diets containing either seven per cent soybean oil or five per cent soybean oil plus two per cent PI. Dietary PI markedly prevented both histological and biochemical markers of liver injury. Additionally, hyperinsulinaemia was relieved by the feeding of dietary PI in rats, suggesting a further benefit of PI as a weight-loss or diabetic agent.

Transphosphatidylated-phosphatidylserine (TPS) is one of the most understudied phospholipids. TPS is a rather novel nutritional supplement, shown in rodent trials to significantly influence cognitive function.17 In a trial from Yakult Central Institute for Microbiological Research, researchers assessed TPS for its effect on learning in mice.17

The trial gave 240, 360 or 480mg/kg TPS following scopolamine-induced learning deficits. The study demonstrated that TPS enhanced learning in a dose-dependant manner, suggesting that behaviour/learning can be significantly influenced by TPS supplementation. Clearly, further work is needed in humans for both application and efficacy.

Brand managers and marketers hold the key
The approved health claim, 'Consumption of phosphatidylserine may reduce the risk of dementia in the elderly,' is a strong point and a major selling factor to the wider consumer base. Approved claims in relation to relaxation, memory enhancement and sports performance are likely to be more lucrative if positioned and branded in the right way.

The old argument of it being an expensive ingredient is not the case as compared to other bioactives offering similar effects, and there clearly is a significant volume of research to substantiate its action and safety. The phospholipid class is currently underperforming given the growth of the fish-oil market, and its future now rests at the feet of the brand manager and the company willing to transition science in consumer-friendly messages.

Mark J Tallon, PhD, is chief science officer of NutriSciences, a London-based consultancy firm specialising in health-claim substantiation, product development and technical writing.
Respond: [email protected]

New derivatives have the potential of being more efficacious than their predecessors — new applications avenues also are drivers

Enhancing Bioavailability
One of the recent effects attributed to phospholipids is their ability to enhance the bioavailability of other nutrients. This has been a significant marketing message for those producing krill as a beneficial source of omega-3 fatty acids. However, little evidence has been available to highlight these claims until recently.

Study 1: In a three-month trial, the conjugation of EPA (250mg/day) and DHA (250mg/day) to PS (300mg) or to triacylglycerol (fish oil; FO) was used to assess the ability of phospholipids to enhance the function and uptake of these fish-oil derivatives in 60 children with impaired visual-sustained attention performance (ADHD).

The results demonstrated that although both supplement forms increased EPA/DHA levels in plasma, only PS enhanced performance in attention tests. The suggested difference was identified where only PC resulted in a significant reduction (~30 per cent) of very-long-chain saturated fatty acids, and an increase in linoleic acid and docosapentaenoic acid.

Study 2: In a trial from the UK, researchers investigated the effects of combining phospholipids with Ginkgo biloba extract (GBE). The current study therefore aimed to assess the comparative cognitive and mood effects of a low dose of GBE or GBE complexed with either PS or PC.

The study utilised a placebo-controlled, multi-dose, double-blind, balanced-crossover design. Participants received 120mg GBE, 120mg GBE complexed with PS, 120mg GBE complexed with PCor a matching placebo. Trials were conducted seven days apart.

In keeping with previous research utilising the same methodology, 120mg GBE was not associated with markedly improved performance on the primary outcomes. However, supplementation of GBE complexed with either PS or PC resulted in improved memory performance, with PS providing the most effective phospholipid. Despite GBE failing in the performance test, when given with PS, PC or alone it was associated with improved calmness.

These trials demonstrate that phospholipids can not only enhance bioavailability of nutrients but also synergistically increase their physiological effect.


1. Souci SW, et al. Food Composition and Nutrition Tables. Stuttgart Medpharm Scientific Publishers. 2000.
2. Louis-Sylvestre J. Phosphatidylserine and memory problems in aged subjects. Cah Nutr Diet 1999, 34(6):349-57.
3. Kidd PM. Attention deficit/hyperactivity disorder (ADHD) in children: rationale for its integrative management. Altern Med Rev 2000;5(5):402-28.
4. Monteleone P, et al. Effects of Phosphatidylserine on the Neuroendocrine Response to Physical Stress in Humans. Neuroendocrinology 1990, 52(3):243-8.
5. Starks MA, et al. The effects of phosphatidylserine on endocrine response to moderate intensity exercise. Int Soc Sports Nutr 2008, 28;5:11.
6. Jäger R, et al. The effect of phosphatidylserine on golf performance. J Int Soc Sports Nutr 2007;4(1):23.
7. Jäger R, et al. Phospholipids and sports performance. J Int Soc Sports Nutr 2007 Jul 25;4:5.
8. Wojcicki J, et al. Clinical evaluation of lecithin as lipid-lowering agent. Phytother Res 1995, 9(8): 597-9.
9. Kn?chel F. Doppelblindstudie bei Patienten mit alkoholischer Fettleber. Med Welt 1979;30:411-6.
10. Sitaram N, et al. Human serial learning: enhancement with arecholine and choline impairment with scopolamine. Science 1978;201:274-6.
11. Von Allw?rden HN, et al. The influence of lecithin on plasma choline concentrations in triathletes and adolescent runners during exercise. Eur J Appl Physiol 1993;67(1):87-91.
12. Olthof MR, et al. Choline supplemented as phosphatidylcholine decreases fasting and postmethionine-loading plasma homocysteine concentrations in healthy men. Am J Clin Nutr 2005;82(1):111-7.
13. Barbagallo Sangiorgi G, et al. alpha-Glycerophosphocholine in the mental recovery of cerebral ischemic attacks. An Italian multicenter clinical trial. Ann N Y Acad Sci 1994 Jun 30;717:253-69.
14. Di Perri R, et al. A multicentre trial to evaluate the efficacy and tolerability of alpha-glycerylphosphorylcholine versus cytosine diphosphocholine in patients with vascular dementia. J Int Med Res 1991;19(4):330-41.
15. Ceda GP, et al. alpha-Glycerylphosphorylcholine administration increases the GH responses to GHRH of young and elderly subjects. Horm Metab Res 1992, 24(3):119-21.
16. Shirouchi B, et al. Dietary phosphatidylinositol prevents the development of nonalcoholic fatty liver disease in Zucker (fa/fa) rats. J Agric Food Chem 2008 Apr 9;56(7):2375-9.
17. Furushiro M, et al. Effects of oral administration of soybean lecithin transphosphtidylated PS on impaired learning of passive avoidance in mice. Jpn J Pharmacol 1997;75(4):447-50.
18. Vaisman N, et al. Correlation between changes in blood fatty acid composition and visual sustained attention performance in children with inattention: effect of dietary n-3 fatty acids containing phospholipids. Am J Clin Nutr 2008;87(5):1170-80.
19. Kennedy DO, et al. Acute cognitive effects of standardised Ginkgo biloba extract complexed with phosphatidylserine. Hum Psychopharmacol 2007;22(4):199-210.

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