Lecithin ••Lecithin has been around for

decades, and hundreds of useshave been developed for it. A

mature market. however. has a down-side. Lecithin producers are currentlydealing with an oversupply whilebalancing lecithin's venerable role asjack-of-all-trades with the more prof-treble value-added lecithin productsof tomorrow.

A mixture of phospholipids,lecithin most of len is derived fromsoybean oil, although other sourcesinclude egg yolk. and brain and livertissues. The principal phospholipidsare phosphatidylcholine (PC), phcs-phatidylclhanoiamine (PE), andphosphatidylinositol (PI). For a fulldescription of lecithin compositionand terminology, take a look atMichael Pamham's article on page1168.

According to Pamharn, the differ-ences in lecithin definitions and spec-ifications around the world are partlydue to the variety of its uses. Lecithinis more a part of daily life than we

This section I\'as prepared by INFORMeditor/writer Tom Krawcz.yk.

INFORM. Vol. 7. 00. 11 (November 19(6)

1159

consider the possibilitiesrealize, from the food we eat to theroads we drive on.

Lecithin can be found in foodproducts such as cake mixes. cheese.candy. chewing gum, chocolate.dehydrated foods, ice cream. instantfoods. pasta. bakery products, mar-garine. and whipped topping.

Lecithin also is used for productsother than food, such as adhesives,adsorbants. animal feed and pet food,catalysts. soaps, cosmetics. paintsand coatings. waxes and polish. inksand dyes, computer printer and pho-tocopier toners. metal processing.explosives. pesticides, fertilizers,plastic and rubber molding. concretecuring. masonry and asphalt prod-ucts. dust-control agents. magneticmedia, leather tanning. lubricants,oil-spill control. textile manufactur-ing, production of plastics, paper pro-duction and coating, wood preserve-lives, and release agents.

What is lecithin?Soybean oil makes up less than 20%

~------------+l~

of the soybean, and less than 3% ofsoy oil is lecithin. If lecithin makes uponly 0.5% of the bean, why evenbother with it?

Lecithin is extracted as a co-prod-uct of the vegetable oil relining pro-cess. where phosphorus-containingcompounds are removed to improveoil quality. As soybean processingincreased. lecithin usually was addedback 10 the meal or to animal feeds.Some oil processors recognized thepotential of lecithin as a mullifunc-tiona I additive for food. feed. andindustrial applications.

"Recovery of lecithin and market-ing of its many modified forms havebecome a part of the economics ofsoybean processing," said FrankOrthoefer. an industry consultant.

Soybean oil is removed from soy-bean (flakes) with a solvent. usuallyhexane. Filtered soy oil can bedegummed by adding water and cen-trifuging the mixture to separate thehydrated gums from the oil. About90% of the phospholipids in oil can beremoved by water degumming.

Wet gums require immediate pro-cessing, as they are high in moisture(roughly 50% water) and will begindecomposing within an hour or two.To process gums to a crude lecithingrade, the wet gums are dried andquickly cooled. Lecithin can bebleached as wet gums between thecentrifuging and drying stages.

The dried gums are in a plasticstate, and can be left in this form orfluidized by adding oil or edible fattyacids to reach viscosities that promoteeasier handling. High-clarity lecithinsare made with more filtering, either inthe miscefla (the mixture of hexaneapplied to soybean flakes and theextracted soybean oil). crude soy oil.or as lecithin.

Additional processing steps areavailable to obtain the necessary qual-ity and characteristics for specificapplications (see "Processing innova-tions," page 1164).

fiers, and 20% (for use) in a variety ofindustrial applications," saidLawrence Johnson, director of theCenter for Crops Utilization Researchat Iowa State University.

Lecithin is a surfactant. which canbe used to create an emulsion of twoor more incompatible substances. Anemulsion is a suspension of smalldroplets of one liquid in another thatis immiscible with the first. Phospho-lipids' hydrophobic fany acid hydro-carbon tails have an affinity for fatsand oils, and phospholipids'hydrophilic polar head groups have anaffinity for water.

The hydrophilic-lipophilic balance(HLB) roughly indicates an emulsifi-er's preference for oil or water.Lecithins can be processed to obtainan HLB of2 (oil-loving) to 12 (water-loving). Low HLB indicates more effi-cient water-in-oil (w/o) emulsificationproperties, and high HLB indicatesmore efficient ojl-i n-water (o/w)emulsification.

The primary usage of lecithin infood is as an emulsifier. For otherfood uses, it softens and retains mois-ture, reduces viscosity, stabilizes, anddisperses. In baking, lecithin com-plexes with gluten proteins as a doughconditioner and acts as a wettingagent.

With a growing trend towardreduced-fat products, lecithin is find-ing a niche of increasing business. Fatremoval from a baked food productformulation may cause loweredlubricity and handling properties,moisture migration, and poor aerationand cell structure. Many of theseeffects can be lessened by incorporat-ing lecithin or a mix of lecithin andother emulsifiers and gums into theformulation.

Lecithin also is used as a releaseagent through its role as a surfactant.Lecithin's edible nature makes it suit-able for use on both cooked products(pan release), and release of foodproducts from conveyor belts in com-mercial operations. Release agentsalso are used to prevent sticking in

(conlinutd on pagt 1/62)

Applications"About 80% of the soy lecithin pro-duced is sold (for use) as food emulsi-

INFORM. Vol. 7. no. 11 (November 1996)

1162

LECITHIN

Lecithin i. Ju.1 one 01 many product. derived lrom processing toybean •.

[continued from page. 1159)

finished food products, such as cheeseslices.

Also used as a biodegradablerelease agent in many nonfood appli-cations, lecithin promotes easier moldrelease from several materials, includ-ing plastics, resins. ceramics, roofingmaterials, and concrete. It also pro-tects the molds from rust and corro-sion.

One of the largest nonfood uses isin calf milk replacers. where it servesin emulsifying, stabilizing, wetting,and dispersing roles, Lecithin alsofunctions as a substrate for enzymesadded to the formula.

Digestibility of nonmilk fats incalves is lower than that of whole-milk fat unless lecithin is added. Evena lecithin content of as little as 2%improves the digestibility of beef tal-low. coconut fat, and lard.

Human nutritionPhospholipids playa part in a widerange of human metabolic processesas well: fat absorption. cholesterolmetabolism. regulating serum lipidlevel, fat transport. blood clotting,nerve function. lung function, biosyn-thesis of prostaglandins, and vision.

The line between nutritional andpharmaceutical uses of lecithin andpurified phospholipids is becoming

more blurred than it has been. Phos-pholipids are used in fields of geri-atrics, fat metabolism, neurology. andliver function, and also in treatment ofconvalescent patients, arteriosclerosis,and certain types of gallstone forma-tion. Research is continuing intoeffects on memory, blood cloning,blood pressure, and vision.

Some of these medicinal uses,however. are in the form of dietarysupplements. Lecithin has been wide-ly available as a retail dietary supple-ment, as capsules or granules. usuallycontaining less than 35% PC. If ahigher PC content is desired, thelecithin must be fractionated.

Mixing deoiled lecithin with alco-hol will separate the lecithin into twophospholipid fractions. While PE frac-tions equally into alcohol-soluble andinsoluble portions, PC is alcohol-solu-ble and PI is alcohol-insoluble. Chro-matographic separation can then beused to prepare polar lipids of thehighest purity.

The American lecithin Co .. whollyowned by Rhone-Poulenc Rorer'sCologne-based Nauermann Phospho-lipid GmbH, markets a 100% PCproduct. The company points to stud-ies that show the amount of PC pres-ent in the brain decreases after age 30.A better studied area is the use of PCas a precursor for acetylcholine, aneurctransmiuer. Brain acetylcholine

levels are sensitive to blood levels ofcholine,

American Lecithin contends that a100% PC supplement provides freecholine in the blood that passes theblood-brain barrier and becomesavailable for the manufacture ofacetylcholine. Other studies havelooked at the role of PC in regulatingdigestive, cardiovascular, and liverfunction.

The roles of choline and lecithin inpromoting health and preventing dis-euse were discussed at the 7th Interna-tional Congress on Phospholipids inBrussels, Belgium. in September. Oneprospect is the designation of a recom-mended daily allowance (RDA) forcholine.

RDAs for vitamins and mineralsare set by the Food and NutritionBoard in the United States. Severalnutrients important to health, such ascholine and folic acid, do not haveRDAs.

The phospholipid congress, spon-sored by the AOCS PhospholipidDivision (international Lecithin andPhospholipid Society) and severalcompanies, focused on the role ofcholine, lecithin, and other phospho-lipids in brain development and mem-ory, decreasing the risks of heart dis-ease and cancer, and cell functioning.

According to Lucas Meyer, anotherphospholipid, phosphatidylserine(PS). is essential to the functioning ofall body cells but is most concentratedin the brain. It is involved in a varietyof nerve cell functions, includingnerve transmitter release and synapticactivity.

Clinical studies have suggested thatPS can support brain functions thatdecline with age. Lucas Meyer hasspent seven years developing a pro-cess to manufacture PS (found at lessthan I% in lecithin) after investigatingthe evidence supporting its use as adietary supplement.

"We've been marketing phos-phatidylserine for about a year and ahalf now," said Susan Gurkin, directorof technical services at Lucas MeyerInc" the U.S. affiliate of Lucas MeyerGmbH in Germany.

"We're laking a different approachwith PS:' Gurkin said. "We're takingthe proactive approach of providing

INFORM. 'Yt>I. 7, no. '1 (NCNefTlber 1996)

the information and educating con-sumers rather than just selling the rawmaterial."

Lucas Meyer plans to do the samething with PC next, Gurkin says, Thatwould put them into competition withAmerican Lecithin's PC product,PhosChol. although they may not beoffered through the same outlets,

"Normally. our product won't befound in a majority of health-foodstores," said Randy Zigmont, presi-dent of American Lecithin. "It takesan educator to explain to the consumerthe difference between PhosChol andan ordinary lecithin supplement."

PhosChol is marketed by AmericanLecithin directly through alternativemedicine providers. The companymarkets the supplement for memoryenhancement. liver protection. andcholesterol reduction, and also forantiulcer effects when used in combi-nation with nonsteroidal antiinflam-mation agents.

As a finished consumer product,PhosChol differs from other AmericanLecithin purified phospholipids thatare for use as raw materials in prepar-ing pharmaceuticals. The companyalso markets commercial-gradelecithin.

"Our mission is to develop purifiedphospholipids for use in pharmaceuti-cal, nutritional, and dermatologicalapplications," Zigmont said. "Phos-pholipids in dermatological applica-tions increase the bio-avaitabillty ofdrugs. enhance skin permeation. andstabilize active ingredients in topicalpreparations."

In pharmaceutical applications,phospholipids can reduce undesirableside effects of new and existing drugs.he said.

PharmaceuticalsPhospholipids can serve as activeingredients in pharmaceuticals by hav-ing an effect on biochemical metabol-ic functions. or as adjuvants (aids)because of their physical-chemicalproperties. Active ingredient researchhas focused on pc, although there isinterest in other phospholipids.

As adjuvants. phospholipids areused as emulsifiers for intravenousinfusion solutions, known as parenter-al solutions. For parenteral solutions.

PC and PE need to be in a specificratio for the emulsion to be stable.

Phospholipids are also used to pro-duce liposomes. Liposomes are closedspherical membranes that, in theirsimplest forms, consist of internalaqueous centers surrounded by twolayers of phospholipids. Again. a spe-cific ratio of PC to PE (80:20) is need-ed to fonn stable membranes.

According to Parnham, PC is theonly phospholipid that forms Hpo-

Powdered (left) and granular(rlghl) deoiled lecithin

somes spontaneously in aqueousmedia. All others require additionalstabilizing compounds 10 prevent thebreakdown of the liposomal structure.

Lipophilic ingredients can beembedded in the fatly regions betweenthe phospholipid bilayer, whilehydrophilic substances are held in theaqueous internal space of the lipo-some. Multilamellar liposomes arccomposed of more than one bilayer.and can allow several compounds tobe compartmentalized.

Liposomes can be used in cosmet-ics to carry moisturizers, sunscreensor tanning agents. vitamins, or fra-grances. The main use to dale hasbeen for skin- and hair-care products.but the hottest growth area is for med-ications. The body absorbs some med-ications more readily when they areadministered in liposome form. Lipo-somes can be targeted for specificorgans. to deliver the drug directly tothe site it is designed for (see lipo-

somes sidebar on page 1166)."There are two sides to our busi-

ness: to supply phospholipids to theresearch community, and to supplybulk material to the pharmaceuticalindustry, mostly for use as drug deliv-ery systems," said Walter Shaw, presi-dent of Avanti Polar Lipids.

According to Shaw. the first phos-pholipid product to hit the drug deliv-ery market was Exosurf, a lung surfac-tant for neonatal babies. "This treat-ment requires the very specific com-ponent of dipalmitoylphosphatidyl-choline," Shaw said. "It won't workwithout it."

Liposomes can do more than justdeliver a drug. though. They can alsolessen the negative effects associatedwith drugs.

"Phospholipids can serve to coverup a toxic drug until delivered to thesite of infection, by use of lipo-somes," Shaw said. "Transportingdrugs in phospholipid membranes orliposomes can lessen the side effectsof a drug."

Shaw said no products are out yet,but gene therapy can be accomplishedby associating a cationic lipid to thegene to be inserted. The lipid helps tocamouflage the genetic material andtransport it across the cell membrane,according to Shaw.

The pharmaceutical market is oneof the few remaining for uses of egglecithin, which was identified longbefore soy lecithin. The compositionof polar lipids and fatty acids in egglecithin is different than thai in soy-bean lecithin, which is advantageousin certain situations. Egg lecithin ismore expensive, however, and isrestricted by other issues as well.

"The FDA has questions about theviral control on egg lecithin. Viral andprotein contamination From soybeanlecithin are not thought to be a threatat this time," Shaw said.

Agricultural chemicalsLiposomes also could be used in agri-cultural chemicals. to promote themixing of compounds that otherwisemight be incompatible. The structureof liposomes also could be valuablefor applying pesticides because of thestructural similarity to biologicalmembranes.

1163

INFORM, Vol. 7. no. II (November 1996)

1164

LECITHIN

Field trials have been conducted onthe effectiveness of using lecithin inagricultural chemicals as both a carri-er (adjuvant) and diluent. Accordingto Johnson, at least four years ofindustry data show lecithin works bet-ter than soybean oil and costs Jessthan comparable petroleum-basedproducts.

"There is no incentive for chemi-cal manufacturers to change (fromthe petroleum-based products),"Johnson said. The efficacy of theactive component is improved, whichwould lead to lesser rates of applica-lion, so the manufacturer would sellless product.

Johnson concedes that farmerslack incentives to become lecithinpromoters. "Since lecithin is such asmall pari of the soybean product,growers are not pushing it," Johnsonsaid. "The lecithin producers are

LecIthIn quallty cen be affected by aoybean growth lind development, as well !III atorageand proclsslng.

Processing innovations: from bean to modified lecithinliitK;:;:i~iil"I think we are going to see a major

change in the oil industry, due tochanges in processing technology,"said Roger Sinram, industry con-suuant. 'There is a push to cut backon the amount of hexane used inprocessing. for example."

Although most soybean proces-sors have been using the same tech-L.:======:J nology for many years to extract

lecithin, there have been some recem innovations, such asthe five described here.

One extraction option being proposed is degumming inthe miscella. Lecithin could be separated out by usingmembranes with pores large enough to allow flow of oiland solvent but small enough to restrict the phospholipids.

Lucas Meyer experimented with membrane materials andfound that plastics may swell and decrease the size of thepores. Ceramic membrane filters are not susceptible toswelling and perform beuer in phospholipid separation tests.

"Membrane technology may even eliminate the refinerstep for soy oil," said Bernie Szuhaj, director of researchand development for Central Soya. Micropore membranetechnology could possibly be used to separate the variousphospholipid fractions in lecithin, according to Sinmm.

Another proposed separation technology is to degumsoy oil with compressed gases. such as carbon dioxide orpropane. Propane does ncr react with lecithin. and could berecovered at room temperature and pressure. Lecithinwould be recovered as a wet sludge by centrifuging the oil.

The lecithin produced is free of oil, with a phopholipidcomposition comparable to lecithin deoiled with acetone.

Although these new ideas in lecithin extraction mayinvolve new technology, the least expensive way to getlecithin out of soybeans is still the tried-and-true methodthat has been used for decades. New methods may havemade it as far as laboratory testing or even pilot-plantscale, but a significant cost reduction or increase in prod-uct quality must occur before companies will switch over.

"While we have looked at various lecithin extractiontechnologies, 10 date we have elected instead to invest inimprovements at other points in our soy processing oper-ations where changes may have more of an impact," saidDon McCaskill, director of the research and technicalcenter at Riceland Foods Inc .• a farmer-owned co-opbased in eastern Arkansas. "We believe our newdehulling system, for example. will give us more long-term benefit for the cost involved."

Not all phospholipids are removed from soybean oilduring water degumming. One proposed alternative inthis area involves using the phospholipase A2 enzyme tohydrolyze the nonhydrntable phospholipids (NHPs) aftersoy oil has been degummed with water. This creates aIysophospholipid that can be hydrated with water andthus removed from the oil by centrifuging.

While proven in a laboratory setting, this technologyis not currently scheduled for use in lecithin production.It is also more of interest to oil producers. to reducephosphorus content in the oil. than to lecithin producers.

The more common method of removing NHPs is to

INFORM. Vol. 7. no. 11 (November 1996)

being incorporated in 1990," Gurkinsaid.

ILPS is working toward standard-ized methodology for the lecithinindustry. According to Gurkin, theEuropean Union recognizes a tolu-lene-insoluble test vs. the familiarhexane-insoluble test in the UnitedStates. The ILPS plans to evaluate allmethods and come up with sugges-tions as a foundation for world stan-dards.

Another difficulty is with Europeanapproval of modified lecithin as foodingredients. Hydroxylated lecithin hasbeen approved for food use in theUnited States for years, but is not cur-rently allowed in Europe. A specific-use petition would be needed to getapproval for use of hydroxylatedlecithin in Europe. Lecithin treatedwith enzymes is now "generally rec-ognized as safe" (GRAS) in the Unit-

morc responsible than soybean grow-ers for any growth in the lecithinmarket:'

According to Johnson, there is alsoa significant difference betweenresearch on soybeans and research onlecithin. Government funding forlecithin research is virtually nonexis-tent, Johnson said.

"Most research in lecithin has beenby the companies that have a vestedinterest," said Roger Sinram, industryconsultant.

StandardsAnother area of difficulty is in indus-try standardization. Nomenclature andtest methods are different around theworld.

"Establishing consistent termi-nology was one of the main issuesleading to the International Lecithinand Phospholipid Society (ILPS)

ed States. but has been legal in Europefor years.

AquacultureOne bright spot for lecithin use aroundthe world is aquaculture. Researchinto marine animal feeding has foundthat three related dietary factors affectthe growth and mortality rate ofshrimp and other crustaceans: phos-pholipids in the diet, choline in thediet, and the proper absorption ofcholesterol.

"Phospholipids are a dietary essen-tial for marine crustaceans, andenhance growth and survival of fishlarvae," said Chhorn Lim, a U.S.Department of Agriculture fishresearch specialist.

Lecithin as an ingredient in crus-tacean diets can address these nutri-tional issues, and also playa function-al role by acting as an antioxidant, a

treat the soybean oil with acid (usually phosphoric or cit-ric). Acid treating may change the composition of thelecithin, however, by increasing the amount of phospha-tidic acid and decreasing the yield of PC, PE, and PI.

The level of NHPs also can be reduced by applyingheat to the soybeans before the extraction process. Thisinactivates the Jipoxygenases and phospholipasesbelieved to cause NHPs during extraction. Tests conduct-ed by Lucas Meyer GmbH & Co. of Hamburg, Gennany,have shown that soybeans receiving this treatment yieldtwice the lecithin as do untreated soybeans, with a higherPC content as well. Overheating the soybeans, however,can increase the level of NHPs.

Beyond crude lecithinOnce extracted, lecithin can be processed further by stan-dardizing, modifying, or fractionating. Simple refiningsteps clarify and remove impurities, but the more importantstandardization of lecithin lowers the viscosity and creates auniform product with a specific phospholipid blend.

Another processing step, deoiling, occurs whenlecithin is mixed with acetone, and acetone-insolublephospholipids are extracted, filtered, and dried. Deoilingseparates neutral lipids from polar lipids, leaving a morereactive lecithin, which enhances the bonding with carbo-hydrates or proteins.

Lecithin can be modified in several ways. Compound-ing combines lecithin with monodiglycerides, emulsifierssuch as glycerol polyelhyleneglycol ricinoleate, dilutionswith special oils such as sunflower or medium-chain

triglyceride oils, or surfactants. Complexed lecithins(blends of lecithin in vegetable oil) are used as releaseagents for process equipment in food manufacturing.

Other possible modifications of lecithin involve acety-lation. hydroxylation, hydrolyzation, and hydrogenation.Acetylation involves a chemical reaction between PE andacetic anhydride, which results in water dispersible N-acyl-PE and acetic acid. The N-acyl-PE helps the remain-ing unreacted lecithin components to disperse readily inwater.

Hydroxylation involves hydrogen peroxide reactingwith the fatty acid carbon-carbon double bonds to formtwo hydroxyl groups at the double-bond sites. Hydroxy-luted lecithin is more suitable for oil-in-water emulsions.Hydrogenation of lecithin, on the other hand, adds hydro-gen to the carbon double bonds, giving greater oxidativestability and reduced solubility.

In lecithin hydrolysis, the same phospholipase A2enzyme that can be used to hydrolyze NHPs left in soyoil is used to selectively cleave the j3~position fatty acidfrom lecithin. This terms Iyso-lecithin, which reacts ran-domly with all phospholipids. Hydrolyzed lecithin is alsoeffective for oil-in-water emulsions.

From raw lecithin extraction to later refining and mod-ifying steps, the processing of lecithin is ripe for innova-tion. "Enzyme-modified lecithin was the last innovativeproduct to be marketed" said Frank Orthoefer, industryconsultant. "Little has been added to commercial pro-cessing in the last 10-15 years. New separation tech-niques have only recently been discussed."

INFORM, Vol. 7, no. II (NCNefTlber 1996)

1165

1166

LECITHIN

binding aid, and by reducing leachingof feed components, according toOrthoefer.

According to the United NationsFood and Agriculture Organization(FAG), aquaculture is one of thefastest growing food production activ-ities in the world. In 1994 (the latestavailable FAD data), fish and shellfishproduction grew over two millionmetric IOns (MT), a leap of 13% over1993 figures.

Global aquaculture production offish, crustaceans, and mollusks hasmore than tripled since 1975. and isexpected to rise to 21 million MT by2000 and 62 million MT by 2025.

Most of that growth. however. isoccurring outside the United States.Asia continues to lead global aquacul-ture efforts, with China, India, Japan,Korea, and The Philippines combiningto account for approximately 80% ofthe total. In 1994, aquaculture produc-lion of fish and shellfish in China con-tributed over 50% to that country'stotal national fishery production. farmore than the United States. whereless than 7% of total domestic fishproduction was from aquacultureoperations.

Yet in the United States, catfishproduction will have jumped tenfoldfrom 1980 levels if predictions of 345MT by 2000 prove correct. U.S. aqua-culture is on the rise, which meansthat the market for fish and crustaceanfeeds is also expanding.

"Much of the aquaculture feedindustry now uses lecithin concen-trates," Onhoefer said.

"Aquaculture is indeed an excitingfield to watch," said Lance Colbert,manager of lecithin technical servicesat Archer Daniels Midland (ADM)Lecithin, which has an aquaculturecenter for research and production."We expect this use of lecithin toincrease."

not thrown away, but sold at a dis-count as soapstock. a mix of soy oilresidues derived from caustic refining,or added back to the soybean meal,where its caloric value increases themeal value.

"It is capital-intensive to separatelecithin, and some are forgoing it(separation) to throw all of the gumsinto animal feed," Sinram said. "Theprocessing, handling, separate tank-age, and logistical hassles make it(lecithin recovery) not worthwhile formany, given that crude lecithin mayfetch only 40 cents (a pound) com-pared to getting 10 cents for the gumsto be used in feed."

These factors play a role inlecithin's growth prospect.

"Worldwide lecithin supplies aregrowing 1-2% faster than demandeach year. so worldwide stocks aregradually increasing," Worrall said."Demand for value-added products isgrowing much more quickly."

Value-added lecithin products mayor may not be a part of your soybeanprocessing business, depending onwhere you are located. "Unlike Europe,North American lecithin companiestend to be integrated with the proces-

The futureThe lecithin industry has room togrow. According 10 Charles Worrall,marketing manager for Central Soya,at present only 40% of the gums insoy oil are convened into lecithin. Inessence, the lecithin market wouldhave to double to utilize currentpotential production capacity.

How could over half of potentiallecithin production be thrown away?The answer lies in the fact that it is

Liposomes may be route to higher-value uses

rJi[i~:;,~~ilOne hurdle to expanding the lipo-some market is that purifying phos-pholipids is expensive. Competingmethods of making active ingredi-ent carriers are to use other materi-als to make liposomcs, or even useother carriers entirely.

"The cost of fractionation is stillan issue, as there is a low level of

L " demand," said Walter Shaw, presi-dent of Avanti Polar Lipids. "As

demand increases, production capacity increases and theprice will decrease. So as the market grows, prices willbecome competitive."

Incorrectly judging the size or timing of the marketmay be enough to sink even the best marketing plans. "Iknow of some in this industry that invested heavily inlarge-scale production and have lost everything," Shawsaid. "h is a real balancing act."

"One reason the cost is high is that for every kilogramof PC you make from lecithin, you generate nine kilo-grams of by-product," said Randy Zigmont, president

and CEO of American Lecithin Co. "Any process thathas a I: 10 ratio of product 10 raw material will be costly.No matter how you look at it, it's going 10 be expensive."

Yet the co-products are not worthless. According toZigmonl, they can be blended back in with other lecithin,but they also have unique properties in their own rights.

"For instance, PE has been shown to exhibit antioxi-dant properties," Zigmont said. "Products derived fromthe by-products (PE and PI) have been shown to increaseyield value in chocolate manufacture."

The limited size of the lecithin market, combined withfew companies working the field, leads to frequent busi-ness partnerships, For instance, Stern Lecithin & Sojahas the responsibility for selling the by-product and foodfractions from Nattennann Phospholipids processing inEurope. Central Soya has those rights for the rest of theworld market.

Another issue holding back phospholipid-based lipo-somes is their stability in cosmetics formulations. Llpo-somes based on other materials or nonliposome polymer-ic capsules can duplicate the feats of liposomes withoutthe restrictions placed on phospholipids.

INFORM. Vol. 7. no. 11 (November 1996)

1167

sors that separate the soy oil from thegums," Worrall said. "Many of thesecompanies produce value-addedlecithin products that extend the func-tionality of the commercial grades."

The world lecithin market, includ-ing all lecithins-all uses, standard-grade through value-added prod-ucts-is 150,000-160,000 MT,according to Worrall. Some in theindustry have suggested that up to120,000MT of the IOtal is standard-grade lecithin.

"Standard-grade lecithin is theworkhorse of the industry," Colbertsaid. "On a percentage basis, it is ourbest-selling product:'

Finding new uses for commercial-grade lecithin is no small task becauselecithin has been on the market sincethe 1950s, so the market is relativelymature.

"Expansion of the standard lecithinmarket has been slow recently," Col-bert said.

Enticing potential users to switchfrom what they are using and to trylecithin is a difficult task at best. Iflecithin gets too expensive for a partic-ular application, users can often substi-tute mono- or diglycerides as emu lsi-

fiers. Still, lecithin is often used as aco-emulsifier by virtue of helping otheremulsifiers work more efficiently.

"Modified lecithins work well inpaints, but so do other things," Sinramsaid. "It will take education, market-ing, and advertising to provide anymomentum away from traditionalsolutions."

"A major growth area in lecithinuse is the aquaculture market, initiallyusing granular or deoiled lecithin,"Orthoefer said. "Shrimp aquaculturehas been growing at more than 35%per year."

"We are constantly looking for newniches," Colbert said. ADM is evenbuilding a new lecithin deoiling plant,based on expected sales.

Central Soya. one of the largestlecithin producers in the industry, hasa partnership agreement with SternLecithin and Soja GmbH. Europe'ssecond largest marketer of lecithin.Stern and Central Soya both areowned by the European firm EridaniaBeghin-Say.

"Both the United States andEurope are major lecithin producingregions of the world," Worrall said."The United States tends to be a net

"Phospholipid stability in formulations is still an issueof concern," Shaw said. "There are a couple of ways toget around this problem. First, you can move from natu-ral products 10 synthetic variations. This allows you tocontrol the number of double bonds rather than just takewhatever nature gives you."

According to Shaw, synthetic phospholipids are mere-ly natural phospholipids where the fatty acids have beenrearranged on the glycerol backbone. This creates a spe-cific profile that determines the physical properties of themolecule.

"Second, ester bonds in the presence of water willhydrolyze:' Shaw said. "ln that case, the hydrolysis canbe limited by using a lyophilized formula and limitingexposure 10 water. A phospholipid can be shipped aspowder, and then sterile buffer is added on site to pro-duce liposomes when needed."

Another factor with liposomes is the limited quantity oflipophilic and hydrophilic materials that can aggregate inthe bilayers and in the core, respectively. "Liposomes canbe given a negative charge, which forces open a widerspace in the center of the liposome. allowing them to take

exporter, and the European Union anet importer, by roughly the sameamount. South America and the FarEast produce smaller amounts." InEurope, much of the lecithin for usein fractionating is purchased fromthe United States, because of thequality and consistency of U.S. pro-duction.

ADM claims to operate the world'slargest lecithin production facility atEuropoort, The Netherlands. Otherlecithin companies associated withADM in Europe are Ohlmiihl Ham-burg and Soya Mainz.

No rnaucr where or how it is made.lecithin will still have a place in theworld today.

"Lecithin is our lowest cost emulsi-fier available now," Orthoefer said."As far as price vs. functionality isconcerned, lecithin is our best alterna-tive."

From roadways to car wax, fromdietary supplements to aquatic feeds,lecithin and purified phospholipidswill continue to fill roles with aunique blend of benefits compared tocost required.

"The future continues to be brightfor lecithin," Orthocfer said.

up more of a hydrophilic drug," Shaw said. "Some chargedltposornes can bind specifically to cell walls or to proteins."

Yet there will always be resistance to change. "Inthe liposome area, phospholipids are competing againstexisting technology that may be cheaper and moreentrenched," said Roger Sinram, industry consultant.

Liposornes have some advantages, however, that can-not be duplicated by alternative carriers. "There are com-peting drug delivery vehicles, but phospholipid lipo-somes are natural products--even the synthetic variationsof them-so 10 metabolize them is easy," Shaw said."Others (drug delivery systems) are not necessarily basedon natural materials, so metabolism becomes problemat-. .,".

Although injectable drug delivery has become theleading research area for lipcsomes. there are otherapplications receiving increased scrutiny. "Liposomesare not restricted to drug delivery, but can be used infoods as well," said Bernard Szuhaj. director of researchand development for Central Soya, "Central Soya isfocusing on food uses, including adding flavors withliposomes."

INFORM. VOl. 7. no. 11 (November 1996)

1168

LECITHIN

The importance of phospholipid terminologyThe name "lecithin" was first used byGobJey in 1850 (I) to describe anextract of egg yolk (Greek lekithos)from which Diakonow (2) subsequent-ly isolated phosphatidylcholine. Sincethat time, "lecithin" and "ph os-pharidylcholine" frequently have beenused interchangeably.

The IUPAC-JUB (InternationalUnion for Pure and Applied Chem-istry-International Union of Biochem-istry) proposals for the nomenclature oflipids provide a systematic definition ofthe chemical structures of pure phos-pholipids and propose a shorthandnomenclature which has found increas-ing acceptance in the biochemical liter-ature (3,4). According to this nomen-clature, 3-511 phosphatidylcholine (PtdCho) is the recommended name forI ,2~diacy l-sn-glycerolt Sjphospho-choline (acyI2GroPCho) (3). The oldtrivial name of "lecithin" is neither rec-ommended nor does it offer any advan-tages over the IUPAC-IUB nomencla-ture (3-5).

However, outside biochemical cir-cles, the term "lecithin" still is usedwidely, frequently without clear defi-nition of what chemical entities theterm is intended to cover. The Inter-national Lecithin and PhospholipidSociety (ILPS) has published the fol-lowing definition for lecithin: "amixture of glycerophospholipids

This article by Michael J. Parnham, Pomhmn Adviserry Services, Van Guericu AUee 4, 0-53125 Bonn,

Germany. and Phannacoiogical11lStihlle for Life sci-entists, Goethe Unil'ersity Franlifun. 0-60439 Frank·fun. Germany, is based on his presentation during the

87th AOCS Annual Meeting & Expoheld earlier this year in Indianapolis. lndiana.

obtained from animal, vegetable ormicrobial sources, containing a vari-ety of substances, such as sphingo-sylphospholipids, triglycendes, fauyacids, and glycolipids" (6). This def-inition covers the wide variety ofnatural and refined lecithin productscommercially available, but does notindicate the relative proportions ofthe different components, nor does itdefine the purification stage of theproduct. Furthermore. the ILPS defi-nition of lecithin clearly would notinclude a synthetic or semisyntheticproduct.

The current regulatory specifica-tions for lecithin and the problemsarising as a result of different con-stituents with varying biological activ-ities will be reviewed briefly and pro-posals made for clear and effectiveterminology.

Table 1Commercial phospholipid fractions from soya beans and their use

Current international lecithin speci-ficationsCommercial lecithin usually isextracted from soybeans or from eggyolk. Crude soya lecithin contains52% mixed phospholipids of which12-18% is phosphatidylcholine.Oeoiling with acetone generates agranular product containing 78%mixed phospholipids (20-95% pbos-phatidylcho1ine) which on furtherextraction with ethanol can be frac-tionated to yield high concentrationsof phosphatidylcholine (7) (Table I).Specifications regarding purity gener-ally reflect the need to limit solventcontamination as well as the presenceof toxic heavy metals and perox.ides.The result is that there is little globalstandardization of the actual con-stituents and physical properties ofcommercial lecithin. This stands in

TYPeCrude lecithin

ContentMilled phospholipids(phosphatidykholine =OillfatsOlycolipidslsugarslothen

Deoiled lecithin

52%12-18%]

35%13%

Milled phospholipids[phosphatidylchcline =01ycolipidsloillfatslothers

78%20-25%]

22%

Ethanol-solublefraction

Milled phospholipids[phosphatidylcholine =

85%40-53%]

Purified phospha-tidylcholine

80-100%

U,.Industrial lubricant,emulsifier

Emulsifier in foods,bread dough stabilizer

Emulsifier in foods.(e.g.. chocolate)

Excipient. liposomes, milledmicelles, active ingredientin cosmetics, emulsifier inphannaceuticals

INFORM. Vol. 7. no. 11 (November 1996)

Table 2U.S., British, Japanese, and European specifications for purity of commercial lecithin

USP XXUJ Merck 1'322 ISCI·IINFXVII Index and EFEMA

Monogruph rcc ru + HPE (11th)

Definition Lecithin Lecithin Lecithin Lecithins Hydrolyzed Soybeanvegetable lecithin phospholipid

Acetone-insolublematter ;<!:50% >50% ;<!:56% """"Hexane-insolublematter ~.3% ~.3% :SO.3Q ~.3%a :SO.3%

Volatilematter <2%' s2 ... ""%

",0 S1.5% S1.5% <2% <2% ""%

A. 3 ppm 3 ppm 3 ppm 3 ppm 2 ppm

Pb SlOppm :SIO ppm SlO ppm :SIO ppm

Heavy metals 40 ppm 40 ppm 50 ppm 50 ppm 20 ppm

Peroxidevalue SIOO SIO SIO slO

Acid value S3. <3. 20-30 <35 <45 S40

Iodine 95-100 95value (liquid)

82-88(gran.)

Packaging well- well-"d closed closedstorage containers containers

a Totuenc.inso-luble.bA1HWCfor t h.

triglycerides, fatty acids, and carbohy-drates in varying proportions. Thespecified product contains 90% ormore of phospholipids of differinggrades, forms. and color. In contrast,the Food Additives Handbook (9)describes lecithin simply as "a com-plex mixture from soybeans, and otherplants." without reference 10 its con-stituents, stating only that in oleomar-garine it is limited to 0.5%.

The US Pharmacopeia (USP XXII)or National Formulary (NF XVII)(10) also provides a similar descrip-tion 10 that of the FCC III, thoughwithout defining the phospholipidcontent or the peroxide value (Table

2). These specifications also are givenin the Handbook of PharmaceuticalExcipients (HPE) published jointly bythe American Pharmaceutical Associ-ation and The Pharmaceutical Societyof Great Britain (II), which defineslecithins from both plants and eggs.The Merck Index (12) specifies aslightly lower acid value (Table 2).The Japanese Monograph (lSCI-IIJ(13) specifies a lower heavy metalcontent.

The European Community specifi-cations (Guideline 78/664IEWG) forlecithins (E322) (14) are also includedin the Monographs far Emulsifiers forFoods (2nd Edition] of the European

marked contrast to purified phos-phatidylchcline which is usually well-defined with regard to source. chemi-cal composition, and physical proper-ties.

The lecithin specifications of theFood Chemicals Codex (FCC IrQ (8)are given in Table 2. The product towhich these specifications refer isdefined as food-grade lecithin fromsoybeans and other plant sources con-sisting of a complex mixture of ace-tone-insoluble phospholipids (mainlyphosphatidylcholine, pbosphan-dylethanolamine, and phosphatidyli-nositol) combined with variousamounts of other substances such as

INFORM. Vol. 7. no. 11 (November 1996)

1169

1170

LECITHIN

Table 3Specifications for commerclallecfthln In German-speaking countries

Monograph DAB 7 OAB PharmacopeiaHelvetica (PH 6)

Definition Lecithin Lecithin Lecithin(egg) (plant) (soy)

Peroxide value S5Acid value :S3 mLbVolatile matters S5% $3% S2%Sulphonate ash <9% 4-7% 4-7%Phosphate ,,% ,,% ,,%Nitrogen 1.7-2.0% 1.7-2.0% 1.7-2.0%Iodine value 55-65 70-90 65-105Packing and storage Well-closed, Well-closed,

light-protected light-protectedcontainers containers

~ AI IOSOC for I h.b Vol. orO.IN NtOH rorOS Ilccilbin in 10 mL ethanol.

Hager'sHandbook

Lecithin(soy)

<5

Lecithin(egg)

<5

3.6-3.9%1.7-2.0%

94-99Well-closed,light-protectedcontainers

<3.8%1.7-2.0%

64-70

Food Emulsifier Manufacturers Asso-ciation (EFEMA) (15). These differ insome respects from the U.S. specifica-tions. E322 distinguishes betweenlecithins (which may be from plantsources or from eggs) and hydrolyzedlecithins. The latter are permitted ahigher acid value and somewhat lowercontent of acetone-insoluble matterthan nonhydrolyzed lecithin, thoughboth European specifications for ace-tone-insoluble matter are stricter thanthose of the Federal Drug Administra-tion (FDA) (Table 2). This alsoapplies to the specification for the per-oxide value, though the U.S. specifi-cations marginally are stricter withregard to water and heavy metal con-tent. E322 also specifies that thelecithin should contain not more than2% volatile matter by drying at 105°Cfor one hour. This presumably is dueto the very different specifications forpharmaceutical use' in German-speak-ing countries (Table 3).

These are predominantly based oncoloring and ashing procedures. In allthree countries [Germany (DAB),Austria (ClAB). and Switzerland (PH6)] the nitrogen content is specified as1.7-2% and the phosphate content asat least 3% (16-18). In Germany (16).arsenic and heavy metal content arenot specified, but the German Regula-tions for the Use of Additives(Deutsche ZusatzstojJverkehrsverord-nung) (19) recommends maximums of

3 ppm for arsenic and 50 ppm forheavy metals in agreement with theE322 specifications. The German For-eign Substance Commission(Deutsche Fremdstoffkommission)(20) recommends an acid value of notmore than 4%. Hager's Handbook(21) quotes the purity specificationsgiven by the USP XXII and theOAB81, but also distinguishesbetween lecithin from egg and soy-beans. The latter is defined as contain-ing approximately 95% phosphatidyl-choline and <1% other phospholipids,while egg lecithin is defined as con-taining approximately 94% phos-phatidylcholine and <2% other phos-pholipids; fatty acid ranges are alsogiven. For both lecithins, Hager'sHandbook provides slightly differingphosphate contents and distinct iodinevalues.

The broad differences in interna-tional specifications also stem fromdifferent traditions in the applicationsof commercial lecithin. On the onehand, the product as a crude prepara-tion may be used as an emulsifier infoods and, on the. other hand, as ahighly purified, biologically activepharmaceutical-grade phosphat idyl-choline.

It is at the level of application thata differentiation in terminology isrequired initially. On the basis of anassessment of the literature since1930, the Life Sciences Research

Office (LSRO) of the Federation ofAmerican Societies for ExperimentalBiology reviewed the use of lecithinobtained from plant sources as ahuman food ingredient (22). and onthe basis of the LSRO report, the FDAsubsequently issued new regulations(21 CRF 1841400) affirming the "gen-erally regarded as safe" (GRAS) statusof plant-derived lecithin (23). (It ispertinent to the present article that theLSRO report drew attention to the factthat the interchangeable use of theterms "lecithin" and "phosphatidyl-choline" "has created confusion," rec-ommending that the trivial name"lecithin" be restricted to the commer-cial product.) When it is used in lowconcentrations as an emulsifier,lecithin's GRAS status covers anypotential biological effects of com-mercial lecithin. However, when high-ly purified components of lecithin areused in larger doses as nutritional sup-plements or as drugs, the biologicalactivity of the product becomes muchmore relevant. In this case, specifica-tions for limitation of impurities mustbe complemented with definitionswhich reflect the desired biologicalactivity, and this may vary dependingon the constituents.

Distinctive biological activities ofphospholipidsNutritional use. Lecithin is used bothas an emulsifier in processed foodstuff's

INFORM, VOl. 7. no. 11 (November 1996)

1171

Table 4Fatty acid composition of soya and egg lecithins, %"

Fatty acids

C16:0C18:0CIS:IC18:2C18:3C20:0

Palmitic acidStearic acidOleic acidLinoleic acidLinolenic acidArachidonic acidO",,~a I'b<:mcqe ollOlal flU)' Kid eonItfIl.

and in high concentrations as a nutri-tional supplement. As an emulsifier,the specific proportions of the phos-pholipids in the lecithin are not crucialbecause it is the physical surfactantproperty of the lecithin, not biologicaleffects, which is of importance for thepreparation of emulsions (24).

A caveat, however, should be drawnfor the use of purified lecithin as anemulsifier in fat emulsions for par-enteral nutrition. Generally speaking,purified egg lecithin is used for thispurpose in North America, and puri-fied soy lecithin has been utilizedwidely in Europe. ln a series of com-parative investigations of fat emulsionsprepared with either egg lecithin(Intralipid) or soya lecithin (Lipo-fundin) as emulsifier, it was found thatlntralipid increased the concentrationof triglycerides in plasma very lowdensity lipoproteins (VLDL), whereasLipofundin lowered VLDL triglyc-eride concentrations (25,26). This dis-tinction can be attributed to the highercontent of polyunsaturated fatty acids(PUFAs) in purified soy lecithin, ascompared to purified egg lecithin(Table 4). An increase in VLDLtriglyceride content is undesirable inpatients at risk for hypercholes-terolemia and atherosclerosis (23). sothat in such patients receiving long-term total parenteral nutrition, thechoice of egg or soy lecithin as anemulsifier may have clinical relevance.It should be noted that both types oflecithin require purification for use inparenteral nutrition. in order to removehemolytic phosphatidic acid.

Lecithin is sold widely as a nutri-

Soya ledthin Egg lecithinKirk-Othmer Hager Klrk-Othmer Hager

(Ref. 27) (Ref. 20) (Rer.27) (Rer.20)

18.4 16-20 37.0 39-474.0 9.0

10.7 8-12 32.3 28-3258.0 62-66 16.7 13-17

6.8 6-85.0 J-<j

2.1 0 1-2

tional supplement. As with parenteralnutrition, oral dietary administrationof egg lecithin results in a higher plas-ma cholesterol concentration thandoes comparable dietary soy lecithin(28). indicating that soy lecithin ispreferable to egg lecithin as a nutri-

tiona! supplement. However, me mainnutritional value of lecithin is as asource of choline. The LSRO report(23) reviewed some of the early stud-ies on the neurological effects ofdietary soy lecithin and phosphatidyl-choline. Subsequent investigations

EDIDLE OIL PROCESSING

NATURALVITAMIN E PLANTS

If you wish to concentrate your Vegetable Oil RefineryDistillate to increase sale value or to manufacture NllturalVitamin E, we have the technology.

We are also specialist in Oleo ~ie.1s ofF.tty Acids.FattyAmiTIes and other derinti\'CS. Pleaseenquire for fullprocess range olTered. We supply packages from simpleupdate of I:Xistingplant through to full plant design orknow-how only

ABLE CHEMICAL & ENGINEERING DESIGN LTDTHE LODGE. NEW MILL., PARK ROAD.DUKINFIELD. CHESHIRE SK16 5LL. UNITED I(INCDOI't1J'bon,t UK 161 ~J 1771, .. _. UK 16. JJU 71U4

For Information cIrcle 1100

INFORM VOl, 7, no. 11 (Ncwembell996)

1172

LECITHIN

Table 5Fatty acid composition of different soya phospholipid classes (%)'"

Fatty acids Phosphatidyl- Phosphatidyl- Phosphatidyl- Phosphatidiccholine ethanolamine Inositol acid

Palmitic acid C16:0 20.5 31.6 47.7 34.0Stearic add CIS:O 5.5 3.2 8.2 8.1Oleic add CIS;) 10.5 8.7 4.9 11.9Linoleic add C18:2 58.8 53.2 36.2 44.7Linolenic acid CIS:3 4 .• 3.2 2.8 1.3

Q Pen:enlll3C oflO11I1fally acid CQf1tent.Reference 49.

have confirmed the importance ofdietary lecithin as a precursor ofcholine and have demonstrated benefi-cial effects of dietary lecithin whenadministered to elderly patients withsome neurological diseases. particu-larly tardive dyskinesia (29.30). In thisrespect. it is not lecithin as a mixtureof phospholipids which is of value.but specifically phosphatidylcholine.In order to relate neurological effectsto the dose or dietary intake. it isessential that the phosphatidylcholinecontent of nutritional supplements beclearly stated.

Phosphatidylcholine and cholineare not only of importance for theneurological health of the elderly. Theplasma of newborn infants has a muchhigher choline concentration than thatof adults (31). Human breast milkwithin the first few days of lactationcontains high concentrations of bothfree choline and other choline-con-taining lipids. including phosphat idyl-choline (32). It has. therefore. beenargued that infant formulas shouldcontain adequate concentrations ofvarious forms of choline. includingphosphatidyJcholine (not just lecithin).to meet the infants' dietary require-ments (32). Once again. the use oflecithin as an emulsifier in infant for-mulas necessitates definition of theproportion of phosphatidylcholine thatis present in order to relate this 10potential biological effects.

Cosmetic IUC. The major use ofphospholipids in cosmetics is in thepreparation of liposomes. These areeither used per se as skin moisturizingagents or as carriers to facilitate skinpenetration of other cosmetic ingredi-ents. Phosphatidylcholine is the onlyphospholipid which forms vesicles

(Iiposomes) spontaneously in aqueousmedia. All other phospholipids requirethe addition of other stabilizing com-pounds to prevent the breakdown ofthe liposomal structure. There isincreasing worldwide pressure toreduce the safety testing in animals ofcosmetic ingredients. and within theEuropean Union such animal testing isactively discouraged (33). Conse-quently. the GRAS status of lecithinusually is invoked to account for thesafety of phospholipids for cosmeticuse and to obviate toxicity testing.

However. phospholipids differ intheir biological effects on the skin.Moisturizing or hydration of skin isachieved by modifying the lipid con-tent of the horny layer (strauoncornea). Administration to normalhuman skin of a liposomal dispersioncontaining 80% phosphatidylcholine.9% phosphatidic acid. and 4% N-acetylphosphatidylethanolamine pro-duced a 38% increase in skin humidity(34). Decreasing the phcsphutidyl-choline content and increasing thephosphatidylinositol content of theIiposomes ultimately resulted in a dry-ing. rather than a moisturizing, effecton the skin. Soy phosphatidylcholine.with a high content of PUFAs. whichare required for healthy skin. may con-tribute toward the regulation of epider-mal proliferation (35).

These effects, while not limitingthe dermal safety of phospholipids.certainly emphasize that the terms"phospholipids," "lecithin," or "lipo-somes" are insufficient to definepotential or expected effects on theskin. For this reason. it is necessary todefine the actual content of specificphospholipids in products applied ascosmetics.

Pharmaceutical usc. Purified phos-pholipids from natural sources.together with semisynthetic and syn-thetic phospholipids, are employed aspharmaceutical excipients and drugcarriers. as well as forming the activeingredients of various pharmaceuticalproducts administered orally, topical-ly. or parenterally. As an excipient. forexample for parenteral diazepam. soylecithin is used in the form of mixedmicelles with bile acid to improve sol-ubility and reduce local irritancy (36).In this respect, it is once again thephysical properties of the phospho-lipids that are most important. sotherefore the content of specific phos-pholipids is not crucial. The relativelysmall amount of product administeredmakes the biological distinctionbetween soy and egg lecithin-asdescribed for parenteral fat emul-sions-irrelevant. However, use ofsaturated. rather than highly unsaturat-ed. soy phospholipids for the prepara-tion of mixed micelles enhances floc-culation and decreases the excipientefficacy of the mixture (37). Conse-quently. even as an excipient. a defini-tion of the degree of saturation of thelecithin used is needed.

Phospholipids also are the basicbuilding blocks of liposomes as drugcarriers. A wide variety of differenttypes of phospholipids. together withadditional charged constituents, pro-teins. and cholesterol are formulatedin liposomes to enhance organ andtissue targeting or to modify transportcapacity (38,39). Quite apart from thefuct that additional charged con-stituents and proteins can exert theirown biological effects. the liposomalformulation of different phospholipidsis not without biological repercussions

INFORM. VOl. 7. no. 11 (Novembef 1996)

1173

Table 6Summary of the comparative properties of commercial lecithin and purIfied phosphatidylchollne

Lecithin

Variable mixture of phospholipidsand other constituents

Cheap emulsifier; degree ofsaturation affects blood lipids;variable source of dietary choline

Inappropriate

Specifications

Nutritional use

Cosmetic use

Phosphalidylcholine

Chemically defined

Standardized degree of saturation;more expensive: standardized sourceof dietary choline and PUFA

Defined moisturizing effect;skin penetration control

Defined excipient; forms liposomesspomcneocsty« Purified from soybeans. usedto treat mild hypercholesterolemia and liver injuryat appropriate dosages

Pharmaceurical use Needs purification: degree ofsaturation affects micelleformation

(40). For instance, the more saturatedthe phospholipid the greater is the len-dency for the liposomes to accumulatein mononuclear phagocytes (41).Moreover. dipalmitoyl phosphatidyl-choline/dimyristoyl phosphatidylglyc-erol (9: I) Hposomes stimulate interfer-on-wtumor necrosis factor c-ecuvaredmouse macrophages. while dipalmi-toyl phosphatidylcholine/phos-phatidylserine (7:3) liposomes areinhibitory (42). Phosphat idyl serinealso has several direct pharmacologi-cal effects on the central nervous sys-tem (43). Even with liposome tormu-lations which are immunostimulatory,the immunoglobulin subtype of anti-body produced differs when usingdipalmitoyl phosphatidylethanolaminerather than dimyristcyl phosphatidyl-glycerol in combination with dipalmi-toyl phosphatidy1choline (42).

Different modes of administrationalso may reveal unusual distinctions inthe biological effects of liposomalphospholipids. Given by intraspinaladministration to rats (a route oftenused clinically for opiate analgesics),for example. dipalmitoyl phos-phatidylcholine. but not soy phos-phatidylcholine. liposomes causedallodynia. a heightened sense of painto normally innocuous stimuli (44).

Several of the direct biologicaleffects of phospholipids per se. whichhave been alluded to previously. haveled to their introduction as pharma-ceutical products. Of all the naturallyoccurring phospholipids detected insoybeans and other plant seeds. phos-

phatidylcholine has the highest pro-portion of PUFA subsrltuems (Table5). Because of its high content ofpolyunsaturated linoleic acid, purifiedsoy phosphatidylcholine exchangeswith saturated phospholipids in circu-lating lipoproteins and is thereforeused as a drug to reduce plasmacholesterol concentrations (45). Soyphcspbatidylcho+ine has also beenused for many years as a drug for thetreatment of liver diseases (46), inaddition to its dietary use in neurodc-generative disease. Recent studiessuggest that it may be of benefit in thetreatment of acne vulgaris (47).

From a pharmaceutical standpoint,therefore. it is crucial to define boththe polar head groups and the fattyacid constituents of both single-phos-pholipid preparations and mixtures, asused in Hposomes, because these char-acteristics can markedly affect bothpharmacological propenies and toxici-ty. Especially as excipients or as drugcarriers, clear definition of the phos-pholipids used facilitates distinctionbetween tested, safe phospholipids, onthe one hand, and synthetic com-pounds with potentially diverging bio-logical activities on the other.

The comparative properties ofcommercial lecithin and purifiedphosphatidylcholine are summarizedin Table 6.

tion not only leads to confusion butalso obscures distinctions in the bio-logical properties of the various con-stituent phospholipids. In foodstuffs, aminimum requirement for a definitionof the source of the lecithin and itsaverage content of phosphatidyl-choline (e.g .• soy lecithin, 25% phos-phatidyJcholine) would cover most ofits commercial applications. Where anadditional process has been introducedthat is likely to have altered the fattyacid content, this should be indicated(e.g .. hydrogenated soy lecithin, 25%phosphatidylcholine). This is in keep-ing with the requirements of the U.S.1990 Nutritional Labelling and Educa-tion Act for definition of the saturated,monounsaturated, and PUFA contentof commercial lecithin (48).

For cosmetic and pharmaceuticalapplications. the term "lecithin"should never be used, either indescribing a product or in specificresearch articles. All too often it isstill possible to find an originalresearch article in which a drug, vac-cine, or other compound is describedas being prepared "in Hposomes"without further characterization. Allphospholipid constituents of cosmeticor pharmaceutical preparations shouldbe described in full with a definition,where possible. of their fatty acid con-stituents (e.g .. dipalmitoyl phos-phatidylcholine or 1,2-dipalmitoyl-slI-glycerol (3) phosphatidylcholine]. NOIonly does this avoid confusion. butassists the interpretation of biologicaleffects observed. Where natural prod-

Conclusions for terminologyThe lax use of the term "lecithin" forthe ingredients of various commercialproducts prepared for human applica-

INFORM Vol. 7. no. 11 (Novembef 1996)

1174

LECITHIN

ucts are used, the degree of purifica-tion should be given (e.g., soy phos-phatidylcholine.95%).

ReferencesI. Gobley, M.. Recherches Cliniques

sur Ie Jaune d'Oeuf, J. Pharm.cu« (Paris) /7:401-417 (1850).

2. Diakonow, C .• Uber die Phospho-rhaltigen Kerper der Hubner- undStoreier. Med. Chem. Untersuch:2..221-227 (1867).

3. IUPAC-IUB Commission on Bio-chemical Nomenclature, Nomen-clature of Phosphorus-ContainingCompounds of BiochemicalImportance, Eur. J. Biochem.79..1-9 (1977).

4. IUPAC-IUB Commission on Bio-chemical Nomenclature, TheNomenclature of Lipids, Ibid.79:11-21 (1977).

5. Silvius, J.R., Structure andNomenclature. in PhospholipidsHandbook, edited by G. Cevc,Marcel Dekker, New York. NewYork and Basel, Switzerland,1993. pp. 1-22.

6. Watkins, T.R, in Phospholipids,edited by J. Hanin and G. Pepeu,Plenum Press, New York, NewYork, 1990, p. 301.

7. Schneider, M., Fractionation andPurification of Lecithin. inLecithins: Sources, Manufactureand Uses, edited by B.F. Szuhaj,American Oil Chemists' Society,Champaign, Illinois, 1989, pp.109-130.

8. Committee on Codex Specifica-tions, Food Chemicals Codex(3rd Edn.), National AcademyPress, Washington, D.C .. 1981.pp. 166-167.

9. Lewis, R.J., Food AdditivesHandbook VNR, New York, NewYork, 1989, p. 773.

10. Committee of Revision, TheUnited States Pharmacopeia(22nd Rev.). U.S. Pharmacopeia!Convention. Rockville. Maryland,1980, pp. 1,572.

11. Handbook of PharmaceuticalExcipients; American Pharmaceu-tical Association. Washington.D.C.. and Pharmaceutical Society.Great Britain, London, 1986, p.165.

12. Budavari. S.• J.O. Neil. A. Smith

and P.E. Heckelman. The MerckIndex (11th Edn.), Merck and Co.Inc., Rahway, New Jersey, 1989,p.854.

13. Yakuji Nippo, Ltd., The JapaneseStandards 0/ Cosmetic Ingredi-ents, 2nd Edition, 1983, p. 418.

14. E322-Lecithins, Official J. Eur.Commun. L 297/31,23.10.82.

15. Monographs for Emulsifers forFoods (2nd Edn.), European FoodEmulsifier Manufacturers Associ-ation, Brussels, Belgium, 1985,pp.I-5.

16. Deutsches Arineibuch (7.Aus-gobe], Deutscher Apotheker Ver-lag, Stuugan, Gennany, 1968, p.150.

17. Osterreichisches Armeibuch (BdII), Verlag der osterreichischenStaatsdruckere, Vienna. Austria,1981, p. 703.

18. Pharmacoooea Helvetica (6thEdn.), Eidgenosslscbe Druck-aachen- und Materialzentrale,Berne, Switzerland, 1971, p. 807.

19. Dt. Zusanstoffverkehrsverord-nung, 20.12. 77 (8. Ges. BLl, S.2653).

20. Dt. Fremdstoffkommission ut«,1.11.67., DFG, Bad Godesberg.

21. List, P., and L. Hcrharnmer, edi-tors. Hager's Handbuch derPharmaeeutischen Praxis (5. Aus-gabe) Bd. 8, Springer Verlag,Berlin, Heidelberg, Germany,1993. pp. 699-700.

22. Wood, J.L., and R.O. Allison,Effects of Consumption ofCholine and Lecithin on Neuro-logical and Cardiovascular Sys-tems, Fed. Proc. 41:3015-3021(1982).

23. Randolph, WF., GRAS Status ofLecithin, Fed. Reg48.-51149-51151 (1983).

24. Dickinson, E., Towards MoreNatural Emulsifiers. Trends FoodSci. Technol. 4:330-334 (1993).

25. Hailer, S., and G. Wolfram. influ-ence of Artificial Fat Emulsifierson the Composition of SerumLipoproteins in Humans, Am. J.C/in. Nut" 43:225-233 (1986).

26. Hailer, S., G. Wolfram and N.ZOllner, Changes in SerumLipoproteins in Humans Follow-ing the Infusion of a Fat Emul-sion Containing Medium- and

Long-Chain Triglycerides, Eur. J.cu« Invest. 17:402-407 (1987).

27. Wendel, A., in Kirk-OthmerEncyclopedia of Chemical Tech-notogy; 4th Edn., Vol. 5, J. Wiley,New York, New York, 1995, pp.192-210.

28. O'Brien, B.C.. and V.G.Andrews, Influence of DietaryEgg and Soybean Phospholipidsand Triglycerols on HumanSerum Lipoproteins, Lipids2&7-12 (1993).

29. Growden. J.H., Use of Pbos-phatidylchoJine in Brain Dis-eases; An Overview, in Lecithin,edited by I. Hanin and G.B.Ansell, Plenum, New York, NewYork, 1987, pp.121-136.

30. Canty, D.J., and S.H. Zeisel,Lecithin and Choline in HumanHealth and Disease, Nutr. Rev.52..327-339 (1994).

31. Zeisel, S.H., M.F. Epstein andR.J. Wurtman, Elevated CholineConcentration in Neonatal Plas-ma, LIfe Sci. 26:1827-1831(1980).

32. Zeisel, S.U., D. Char and N.F.Sheard, Choline, Phosphatidyl-choline and Sphingomyelin inHuman and Bovine Milk andInfant Formulas, 1. Nutr.116..50-58 (1986).

33. Loprieno, N., Guidelines forSafety Evaluation of CosmeticsIngredients in (he EC Countries,Food Chem. Tosicol. 30:809-815(1992).

34. Artmann, C; 1. Reding, M. Ghy-czy and H.G. Pretzel, Influence ofVarious Liposome Preparationson Skin Humidity, ParfiimerieKosmetik 5:326-327 (1990).

35. Bonnekoh, B., and G. Mahrle,Cutaneous Application of Lipo-somes-A Survey of the litera-ture with Special Regard 10 DataConcerning Keratinocytc Cul-tures, Animal Experiments, andClinical Studies, H+G Z Hauti-rankh. 65:99-105 (1990).

36. Mattila, M.A.K., and M. Suistorn-au, Intravenous Premedicationwith Diazepam. A ComparisonBetween Two Vehicles. Anaesthe-sia 39:879-882 (1984).

37. Durr, M., J. Hager and J.P. Lchr,Investigations on Mixed Micelle

INFORM,Vol. 7, no. 11 (November 1996)

1175

and Liposorne Preparations forParenteral Use Based on SoyaPhosphatidylcholine. Eur. f.Pharm. BiopJwrm. 40:147-156(1994).

38. Oregoriedls. G .. Overview of Lipo-somes. J, Antimicrob. Chemother:28 Suppl 8:39-48 (1991).

39. Lesic, D., Liposomes. Amer. Sci.80 ..20-31 (1992).

40. Pamham. M.J" Do PhospholipidsHave Toxicological Limitations",in Phospholipids: Characteriza-tion, Metabolism. and Novel Bio-logical Applications. edited by G.Cevc and F. Pelrauf AOCS Press,Champaign. Illinois, 1995, pp.56-66.

41. Allen, T.M., L. Murray, S. MacK-eigan and M. Shah, Chronic Lipo-some Administration in Mice:Effects on ReticuloendothelialFunction and Tissue Distribution,J, Pharmacol. Exp. Ther.229..267-275 (1984).

42. Phillips. N.C., and L. Gagne. Mod-ulation of Murine MacrophageNitric Oxide Synthesis by Liposo-mal Phospholipids: Correlationwith Liposome Immune AdjuvantActivity. J. Drug Targeting3..137-147 (1995).

43. Toffano, G., and A. Bruni. Phar-macological Properties of Phos-pholipid Liposomes, Pharmacal.Res, Commun, 12:829-845(1980).

44. Yanez. A.M .• M.S. Wallace. D.O.Shen, R.J. Y. Ho, T. Bui and T.L.Yaksh, Use of Liposomes forSpinal Delivery of Alfentanil inRats, Abstracts 7th WorldCongress on Pain, Paris, France.August 22-27, 1993, p. 220.

45. Oette, K.• On the Administrationof Phosphatidylcholine-Metabolic and PharmacokinetleAspects in Humans. in 50thAnniversary of PhospholipidResearch (EPL), edited by K.J.Gundermann and R. Schumacher,wbn- Verlag, BingenlRhem, Ger-many. 1990, pp. 35-48.

46. Kuntz, E.. The "Essential" Phos-pholipids in Hepatology-50Yean; of Experimental and Clini-cal Experiences, in 50lh Anniver-sary of Phospholipid Research(EPL). edited by K.J. Gunder-

47.

mann and R. Schumacher. wbn-Verlag, BingenlRhem. Germany,1990, pp. 49--68.Ghyczy, M., Phospholipon andNatipide II: The Treatment ofAcne Vulgaris by Phosphatidyl-choline from Soybeans. with aHigh Content of Linoleic Acid. inA Mirror of Continuous Research,

edited by E. Hoff. NattermannPhospholipid, Cologne. Germany,1995. pp. 65-73.

48. ILPS White Paper, Lecithin andthe Nutritional Labeling Act,INFORM 6..194-195 (1995).

49. Pardun, H., Die Pflantsnlecithine,Verlag fur chemische Industrie H.Ziolkowsky, Augsburg, 1988. •

iSOLUTIONS FOR HEATING IN

EDIBLE OIL PROCESSING

95 BAR-HIGH-PRESSURE

NATURAL CIRCULATION BlIJILER

The executivemanufacturer ofboiler forhermetically closedsteam systems up to95 bar (1350 psi),3025 kW(lOx 10' BTU/H)for Edibles OilsIndustry processheating.

., .,

Advantages withGEKA: more than25 years experience,approved systems,worldwide in theEdible Oi/lndustry.

GEKA ENERGY SYSTEMSGOTTFRIEDKNEIFELGmbH & Co. KGGermany. Dieselstra8e 80-76227 Karlsruhe-Dur/achTEL: 49-721194374-0FAX: 49-721/494331

For Inlormation circle 1\ 11