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74 Grasas y Aceites Vol. 51. Fasc. 1-2 (2000), 74-96

Lipids in pharmaceutical and cosmetic preparations

By Antonio M. Rabasco Alvarez and María Luisa González Rodríguez

Facultad de Farmacia, Universidad de Sevilla, C/ P. García González, s/n. 41012 - Sevilla, SPAIN.

RESUMEN 1. INTRODUCTION Lípidos en preparaciones farmacéuticas y cosméticas The word «lipid» comes from the Greek word lipos, meaning fat greasy to the touch. Lipids are En el presente trabajo se ha llevado a cabo una revisión diverse group of organic compounds found in plants, sobre las aplicaciones de los lípidos en el campo famacéutico. animal and micro-organisms. They comprise one of En un primer apartado, se describieron los diferentes lípidos the three large classes of foods and, with proteins utilizados como excipientes en cosmética y medicina. En este sentido, se utilizan muchos aceites vegetales, como el aceite de and carbohydrates, are components of all living cells. almendra, albaricoque, aguacate, borraja, café, cártamo, etc.; a According with Bloor's concept, lipids can be partir de fuente animal, pueden emplearse como excipientes en defined as one of the major classes of biological formulaciones cosméticas los aceites de pescados y de aves. substances constituting a cell. Some lipids are También se utilizan con este propósito las grasas y las ceras. Así mismo se revisan los fosfolípidos empleados en cosmética y en completely insoluble in the water of the protoplasm diagnosis, que actúan como vehículos transportadores de while dispersing themselves throughout in the form of sustancias activas, como los liposomas. tiny droplets in other cases as certain chemical Finalmente, se llevó a cabo un estudio de los lípidos, en groups attached to the lipids apparently bind them to función de su actividad biológica, como sustancias activas que the water molecules. Lipids like lecithin and cephalin, forman parte de la elaboración de formulaciones cosméticas, farmacéuticas o suplementos nutricionales. Los carotenoides, which are soluble in water and fats, serve a vital role retinoides y tocoferoles son usados por sus propiedades in the cell by binding water-soluble compounds such antioxidantes, importantes para la salud y la medicina preventiva. as proteins to lipid-soluble substances. In lipid droplets energy storage is more efficient PALABRAS-CLAVE: Cosmética — Excipientes — Lípidos — because the molecules are concentrated into a small Medicina — Suplemento nutricional. area. Also, lipids are better than carbohydrates for energy storage because the carbons on the acyl-chains of the lipids are in a highly reduced state, which maximises the energy per mole given off when those carbons are oxidised into carbon dioxide SUMMARY and water. Carbohydrate carbons are already partially oxidised, and therefore give off less energy. Lipids in pharmaceutical and cosmetic However, for decades, progress in lipid preparations chemistry lagged well behind that in other major In this paper, a review of the applications of lipids in the biological substances, most notably carbohydrates pharmaceutical field has been reported. and proteins. Two principal reasons have been In a first stage, different lipids used as excipients in pointed out. First, it was more simple and easy to cosmetics and medicines have been described. Many vegetable device laboratory methods for handling carbohydrates oils are used in this sense: almond oil, apricot oil, avocado oil, borage oil, coffee oil, safflower oil, etc.; from de animal source, and proteins; fats and substances closely fish oil and bird oil can be employed as excipients in cosmetical associated with them were generally amorphous, formulations. Fats and waxes may be also used for this purpose. and they were distressingly difficult to separate into A broad range of phospholipids are suitable for use in cosmetics, individual components by methods commonly pharmaceuticals and diagnosis. These substances are used as employed in organic chemistry in the early part of vehicle for therapeutic substances, such as liposomes. Finally, a study of lipids, as a function of their biological this century. Second, the principal lipid substances, activity, as active substances for the elaboration of mainly triacylglicerols in fats and oils, were pharmaceuticals, cosmetics or nutritional supplements, was considered to be relatively inert biologically, serving carried out. Carotenoids, retinoids, tocopherols are used for their primarily for storage of energy that could be drawn antioxidant properties, that are important to health and diagnostic medicine. upon as needed. Thus, in general, there was little interest in research to discover the properties, KEY-WORDS: Cosmetic — Excipients — Lipids — Medicine structures, biosynthetic pathways, biological — Nutricional supplement. utilisation, and functions of triacylglicerols, and of Vol. 51. Fasc. 1-2 (2000) 75

qualitatively less abundant or even unusual lipids properties and performance characteristics. New (Lundberg, 1984). vegetable oils are near commercial introduction. Lipids discussed in detail in this study are Since lipids appear to be on the verge of triglycerides and their derivatives, fatty acids and renaissance, it will be critical to assess the market their derivatives, natural plant and animal waxes, and opportunities for the new technologies and products phospholipids. Also mentioned are sphingolipids, and to understand the forces for change in the years carotenoids, tocopherols and other types of lipids. ahead (Rotheim, 1997).

2. LIPID FUNCTIONS 3. CLASSIFICATION

Lipids possess important functions at very Because very little was known until after the turn different facets. They are indispensable for all the of the 20th century about the vast number of living beings, since they exercise important plastic, different classes of lipid compounds, no serious energy and metabolic functions. They have also, attempts had been made to classify lipids. numerous applications in Nutrition and Dietary, Lipids can be classified in many ways, due to Food Science, cosmeticals, pharmaceuticals, paints their different composition, nature and origin. and varnishes, detergents, etc. According with Bloor's classification, lipids can be The Food and Agriculture Organisation of the divided in: simple lipids, compound lipids and United Nations (FAO) and the World Health derived lipids. Individual characteristics are not Organisation (WHO) have listed five of the most discussed in this section because they are well important functions of dietary fats as follows: as a known. In tables I and II, the most important lipids source of energy (obtaining primarily carbon dioxide and fatty acids are collected. and water in their ultimate conversion), for cell The structure of simple lipids are like chain-like structure and membrane functions (lecithin is an molecules consisting of hydrogen, carbon and important structural component of the cell membrane, oxygen alcohol known as glycerol (glycerine) and where it maintains continuity between the water and the fatty acids. They are combined to make up lipids phases inside and outside the cell), as a source these simple acids. They release more energy of essential fatty acids for cell structures and when burned in the cell than any of the other prostaglandin synthesis, as a vehicle for oil-soluble substances in the cell. However, they are not easily vitamins (A, D, E and K) and for control of blood lipids. burned as sugars, hence they are stored in cells as The role of fats in relation to cholesterol metabolism reserve sources of energy found in abundance in and cardiovascular disease (atherosclerosis, coronary the cells as fatty tissues. thrombosis and cerebral haemorrhage) has a long Compound lipids yield «other substances» upon and controversial history. Many questions still hydrolysis besides alcohol and fatty acids. remain about the roles that fats play in these Derived lipids include steroids, fat-soluble phenomena in relation to the structures of dietary vitamins, prostaglandins, etc. fatty acids (Leaf, 1996). There have been many recent developments relating to complexes where lipids and proteins are held together by forces of the 4. LIPIDS AS EXCIPIENTS IN COSMETICS AND van der Waal type, as in lipoproteins. It now MEDICINES appears that there is a good correlation between the incidence of cardiovascular disease and the blood In this section, we are going to describe the most levels of high density lipoproteins (HDL), or the ratio useful lipid substances that are used as excipients of high density and low density lipoproteins in pharmaceutical and cosmetical preparations. In (HDL:LDL) (Siess, 1999; Weber, 1999). many cases they are used indistinctly in cosmetic From another viewpoint, lipids were once the formulations and in pharmaceutical products. For primary sources of aliphatic carbon compounds that reason, it is difficult to establish a clear division used by industry. With the arrival of petroleum, the between them. consumption of lipids declined in most industrial applications, although obviously they still retain their strong position in foods and feeds. 4.1. Simple lipids Today, market forces, regulations, and concerns about the environment once again bring lipid 4.1.1. Triglycerides materials to the fore, as an alternative to petrochemicals (Shimada, 1999). At the very same Triglycerides are esters of trihydroxy alcohols time, new technologies have come along to create with three fatty acid molecules. They are the new and modified lipids and to introduce new principal components of oils and fats. 76 Grasas y Aceites

Table I Classification of lipids

Almond, apricot, avocado, borage, canola, castor, coffee, corn, evening primrose, Oils Vegetable oils macadamia, olive, safflower, sesame, Triglycerides soybean, walnut, wheat germ Simple lipids Animal oils Black Sea dogfish, emu, sardine, shark liver

Fats Cocoa, coconut, palm, shea butter

Waxes Bees wax, jojoba, lanolin, spermaceti

1,2-Dimyristoyl-sn-glycero-3-phosphate (DMPA) Phosphatidic acids 1,2-Dipalmitoyl-sn-glycero-3-phosphate (DPPA) 1,2-Distearoyl-sn-glycero-3-phosphate (DSPA)

1,2-Dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) 1,2-Dipalmitoyl-sn-glycero-3-phosphoglycerol (DPPG) Phosphatidyl glycerols 1,2-Distearoyl-sn-glycero-3-phosphoglycerol (DSPG) 1,Palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG)

Diphosphatidyl glycerols

1,2-Dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE) 1,2-Dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) Phosphatidyl ethanolamines Phospholipids 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine(DOPE)

1,2-Dilauroyl-sn-glycero-3-phosphocholine (DLPC) 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) Compound lipids 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) Phosphatidyl cholines 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC) 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC) 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)

Phosphatidyl serines

Phosphatidyl inositols

Phosphone analogs

Egg sphingomyelin (ESM) Sphingophospholipids Sphingomielins N-palmitoyl sphingomyelin (C16SM) Sphingolipids N-stearoyl sphingomielin (C18SM)

Cerebrosides Sphingoglycolipids Gangliosides

Glycolipids

Sulfolipids Sulfogalactolipids

Sterols and sterol esters Cholesterol, cholesterolstearate Derived lipids Steroids Sterylglycosides and acylsterylglycosides Vol. 51. Fasc. 1-2 (2000) 77

Sterol sulfates

Steroids Bile acids and their conjugates

Carotenoids A Derived lipids Retinol Fat-soluble D vitamins E

K Tocopherols

Prostaglandins PGA2, PGB2, PGE2, PGF1α, 6-keto-PGF1α, PGD2, PGH2, PGI2, U-46619, 11-β-PGF2α

Table II Classification of fatty acids

Caprylic (8:0) Lauric (12:0) Saturated Myristic (14:0) Palmitic (16:0) Stearic (18:0)

Monounsaturated Oleic

9(S)-HODE

Linoleic 9(S)-HPODE

13(S)-HODE

Linolenic

Dihomo-gamma-linolenic

Arachidonic

Unsaturated Eicosapentaenoic (EPA) Polyunsaturated Docosahexaenoic (DHA)

Eicosatetraynoic (ETYA)

Eicosatrienoic

Eicosatriynoic (ETI)

Eicosa-8,11-diynoic (EDYA)

Cerebronic

Vernolic

Hidroxi- Licanic

Epoxi- Lactobacillis

Keto- Sterculis

Cyclopropane- Chaulmoogric

Cyclopropene-

Cyclopentenyl-

Furane- 78 Grasas y Aceites

Fats and oils are water-insoluble substances of characterized as a pale yellow, clear oil having a plant or animal origin that consist predominantly of very mild, sweet, nutty odor and taste. Prized by triglycerides. Those that are solid or semisolid at aromatherapists as one of the best carrier oils, it is room temperature are normally called fats, while used in cosmetic preparations as a moisturizer and is those that are liquid under the same conditions are reported as such excessively dry skin, sunburn, wind called oils. burn and under certain conditions as an antioxidant The European Union, the United States, and the to preserve other natural ingredients. This oil is a People's Republic of China are the largest markets, good emollient because of its high unsaturated fatty together accounting for over 40% of world acid distribution. It can cause inestability problems consumption; India, the former USSR, Brazil, and in cosmetical preparations. It is used in infant Japan account for another 20% of the total; other formulations, lip balms, creams and it makes a regions and countries make up the remainder. pleasant soap. This oil is also used as an ingredient The European Union countries, which together for preparing microcapsules (Esquisábel, 1997). account for more than 16% of global consumption, APRICOT OIL: Apricot oil is the mechanically are the world's largest consumers of fats and oils, expressed oil from the ripe fruit of the tree Prunus requiring net imports of 15-20% to meet demand. armeniaca, which is a member of the Rose family. Animal fats, soybean oil and rapeseed oil are the This oil is characterized as a pale yellow, clear oil three dominant products, accounting for over 50% having a very mild odor and taste. It has a high of the EU market. This region is the world's largest percentaje of oleic acid (Girgis, 1998). This is a producer of olive oil, supplying 77% of the market. light, soft oil often used alone in massage. It is also The United States has about 13% of global used in toilet soaps, lip balms and creams. demand; soybean oil and inedible tallow and grease AVOCADO OIL: It is the centrifuge extracted oil together constituted more than 60% of U.S. from the fruit of the tree, Persea americana (also consumption. Growth in overall U.S. demand for the classified as Persea gratissima), which is a member next five years is expected to be modest, although of the Lauraceae family. The avocado is native product substitution of those oils with low levels of to the tropical regions of Mexico and Central saturated fats (e.g., canola oil, sunflower oil, olive oil) America. Avocado oil is clear, and predominately will continue to displace oils with high levels of monounsaturated giving it excellent oxidative saturated fat (e.g., palm oil and coconut oil) in the stability. It is light and nontacky with quick edible vegetable oil market. Nonfood markets penetration characteristics. The odor and flavor of accounted for 27% of total U.S. demand in 1992, with this oil are of a very pleasant, faint nutlike tone. It is animal feeds, fatty acids, soap, drying oil industries, used as emollient, protector and regenerator. All plastics and resins, and lubricants and greases the these actions seem to be as a consequence of its main nonfood applications (Zuanich, 1998). unsaponifiable matter. It is possible to find avocado oil in expensive creams and lotions, baby soap and 4.1.1.1. Oils shaving soap. B : It is derived from the seed of borage They are liquid products obtained by different ORAGE OIL (Borage officinalis). Borage oil is sought after for its techniques from the fruit of some vegetables or content in unsaturated fatty acids. This oil also some animal organs. They are principally contains 1 to 2% unsaponifiables.In capsules, constituted by triglycerides; they also contain borage oil is often recommended to treat skin and another lypophilic substances in low proportions, what's this mean? problems: it is used to prevent such as fatty alcohols, hydrocarbures, fatty acids, ageing and wrinkles, to fight dehydration and the vitamins, phytosterols, etc. These last components loss of skin elasticity (gamma-linolenic acid plays determine in many cases their cosmetical and the essential role). Borage oil has regenerative, pharmaceutical activity. firming and restructuring properties. It is thus a worthwhile ingredient in products for dry, damaged Vegetable oils or tired skin and in products for dry or permed hair. The principal constituents of vegetable oils are It can be used in any cosmetic product as an active esters of glycerol and fatty acids along with partially principle or as a carrier in the oily phase, without glyceridic material such as lecithin and substances any proportion limit (Tolleson, 1993; Henz, 1999). such as tocopherol. Their composition will vary CASTOR OIL: It is a fixed oil obtained from the according to the species and the use will depend seeds of Ricinum communis and contains 80% especially upon the variety, type and proportion of ricinoleic acid triglyceride (Wilson, 1998). It is used fatty acids. as an occlusive skin conditioner and solvent in ALMOND OIL: Sweet almond nut oil is the mechanically products such as lipsticks, eye and face makeup expressed oil from the ripe fruit of the tree Prunus and nail polish. Lipsticks dermatitis related to castor dulcis, which is a member of the Rose family. It is oil were reported (Andersen, 1984; Wakelin, 1996). Vol. 51. Fasc. 1-2 (2000) 79

This oil is classified as an oleaginous vehicle and is recommended ingredient in nourishing shampoos for present in some topical pharmaceuticals, dry hair, moisturizing creams for dry skin and baby intramuscular injectables and solid oral dosage skin, restructuring creams for around the eyes for forms (Montousse, 1999). Its high viscosity makes mature skin, hand creams and lip balms (Ako, 1995). difficult its use in some cosmeticals, but through OLIVE OIL: This oil is the fixed oil expressed from the ethoxylation become non ionic surfactant having fruits of the tree Olea europaea. The major constituents good solubilizing properties for oils. Polyethoxylated are triolein, tripalmitin, trilinolein, tristearate, castor oils are used in cosmetics as a perfume, in monostearate, triarachidin, squalene, β-sitosterol alcoholic vehicles as a volatile oil solubilizer, and in and tocopherol.Olive oil is used as a solvent and skin hand lotions as a substitute for castor oil. PEG and hair conditioner in cosmetics. Types of products hydrogenated castor oils are used in aftershave include shampoos and hair conditioners, cleansing lotions, cleansing products, skin fresheners, products, topical creams and lotions and suntan colognes, hair tonics and other cosmetics with products (Smolinske, 1992). It is a potent fatty acid alcoholic vehicles. Polyethoxylated castor oil penetration enhancer (Loftsson, 1997). Olive oil is (Cremophor®) is used as an emulsifier and an oleaginous excipient used in oral, topical and solubilizer in pharmaceuticals containing volatile parenteral solutions. oils, fat-soluble vitamins and other hydrophobic SAFFLOWER OIL: It is the expeller pressed oil from substances. Hydrogenated castor oil is used in the seed of the plant Carthamus tinctorius, which is some solid oral dosage forms and topical creams classified by many as the world's most ancient crop. It (Smolinske, 1992; del Arco, 1997). is characterized as a pale yellow, clear oil having a COFFEE OIL: It is derived from the seeds (beans) very mild, nutty odor and taste. Regular Safflower oil of species of trees belonging to the Rubiaceae (linoleic safflower oil) approximately contains 75-80% family, genus Coffea. Of the more than 30 species, linoleic acid. This high percentage makes difficult its only 3 are of important commercial value: the utilization in some preparations. So, it is possible to Arabian (Coffea arabica), the Robusta (Coffea treat it to convert linoleic acid to oleic acid (oleic canephora), and the Liberian (Coffee liberica). safflower oil), that demonstrates excellent oxidative Coffee oil is derived from exclusively the Coffea stability in cosmetic formulations. Safflower is very arabica species, which is considered by most to be rich in essential fatty acids which are important for the finest species of coffee in the world. Coffee oil the integrity of the skin tissues. These essential fatty has demonstrated excellent skin feel properties due acids bring to the cell membrane essential to its fatty acid profile character (Tisnes, 1992). structuring components which are not synthesized However, even more interesting is its ability to block by the skin and constitute a reserve in which the solar radiation from the 280 to 320 nanometer range skin cells draw its nourishment. It is absorbed which causes erythema, but at the same time allows rapidly in the skin epithelium where the nourishing radiation (320 - 400 nm) to pass which tans the skin. benefits of polyunsaturated triglycerides can be This function is believed to be caused by free utilized. Safflower oil is used on the skin as a unsaponifiable materials naturally inherent in the oil replacement for mineral oil which is reported to known as caffestol and kahweol, and monoesters of desolve vitamin A in the skin. caffestol and kahweol (Pons, 1995). SESAME OIL: It is the expeller pressed oil from the CORN OIL: It is obtained from the seeds of Zea mais seed of the plant Sesamum indicum, which is a by extraction with solvent. This oil possesses a high member of the Pedaliaceae family. This oil is content in unsaturated fatty acids and it has been very characterized as a pale yellow, clear oil having a very used for the production of bar soaps (Delaveau, 1971; mild, nutty odor and taste. It has been produced for Pons, 1995; Hasson-El-Mallah, 1999). thousands of years and is considered the «queen» of MACADAMIA NUT OIL: This oil is the expeller pressed oils because of its stability and lack of impurities. oil from the ripe fruit of the tree Macadamia ternifolia. Sesame oil contains powerful, natural antioxidants It is characterized as a pale yellow, clear oil having a (sesamin, sesamol, sesamolin, and phytosterol) very mild odor and taste. Macadamia nut oil is one of which give the oil very good oxidative stability. the highest plant derived sources of palmitoleic acid, Sesame oil is very stable and resistant to oxydation which protects the cell lipids against peroxidation. and it can bestow this property on other cosmetic This essential fatty acid is mostly found in fish oils, in components thus making it a natural preservative. It such high quantities is rarely found in vegetable oils. has pronounced regenerative action due to its high Given its high content in essential fatty acids, unsaponifiable content. Effective in countering ill macadamia nut oil has restructuring properties: it effects on the skin resulting from aging, sesame oil strengthens the skin lipidic barrier and thus improves has been reported to have healing effects on certain the skin moisturization. It has emollient and skin conditions such as eczema, seborrheia, regenerative properties and is an adequate skin psoriasis and sunburn. Sesame oil is used as a conditioner. Due to these properties, it is a solvent and skin and hair conditioner in cosmetics. 80 Grasas y Aceites

Types of products include makeup foundations, WALNUT OIL: It is the expeller pressed oil from the lipsticks, eye makeup and hand and body creams ripe fruit of the tree Juglans regia, which is and lotions. It is present in some parenteral commonly known as the white or English walnut. It pharmaceutical products (Ten Wolde, 1997; Esquisábel, is characterized as a pale yellow, clear oil having a 1997) and there are also several oral capsules, large percentage of linoleic acid. Due to its high emulsions, tablets and topical creams containing this content in unsaturated fatty acids, shows low excipient (Smolinske, 1992). Alveolar carcinoma was stability properties, limiting its use in cosmeticals. reported in an elderly man who used sesame oil WHEAT GERM OIL: It is the extracted oil from the continously to lubricate his tracheal cannula germinated seeds of Triticum sativum. This oil (Maesen, 1985). It has also been reported contains phospholipids and an unsaponifiable with hipersensibility to sesame oil in foods and cosmetics a high content in carotenoids and tocopherol. It is (Pecquet, 1998; Stern, 1998). frequently used as nutritious active ingredient for SOYBEAN OIL: Soybean oil is the refined fixed oil the care of the delicate and sensitive skins (Pons, obtained from the seeds of Glycine soja. Constituents 1995). are primarily triglycerides of oleic, linoleic, linolenic Another oils are: Tomato seed oil, that was found and saturated acids. Soy protein residues are not to contain high levels of linoleic (Lazos, 1998), consistently present in refined soybean oil. Less pumpkin oil, which fatty acid composition showed purified derivatives, such as some cold-pressed that the predominant were linoleic (42%) and oleic soybean oils, may contain soybean proteins. This (38%) (Tsaknis, 1997), peanut oil, cottonseed oil, etc. oil is used for its emollient properties in bath oils, Finally, as a summary, some cosmetic applications shampoos and hair conditioners, cleansing of vegetable oils are collected in table III. products, creams and lotions, and suntan products. It is also used in pharmaceuticals (Asai, 1999). Fish oils Intravenous fat emulsions used in parenteral nutrition (Intralipid) contain soybean oil, egg yolk Fish marine oils are produced from the body or phospholipids, glycerol and water for injection the liver of the fish. Fish lipids provide an ideal and (Turco, 1987). Soybean oil oxidative studies were natural source of the essential fatty acids, EPA, carried out to evaluate the oxidative stability of DHA and DPA (Nieto, 1997). The consumption of soybean oil triacylglycerols obtained from fish lipids provides the body with a direct source of genetically modified soybeans. Oxidative stability the ω-3 series of fatty acids bypassing the need to was improved due to the modification of the fatty convert alpha-linolenic acid to EPA and DHA. acid composition in which polyunsaturated acids Numerous studies have shown that ω-3 fatty (such as linolenic and linoleic acids) were acids help lower cholesterol and blood triglycerides, decreased and in which monounsaturated fatty and help prevent clots in arteries which may result acids (such as oleic) and saturated acids (palmitic in strokes, heart attacks and thromboses. EPA is and stearic) were increased (Neff, 1999). Another used as pharmaceuticals, due to its effectiveness at study has been carried out to determine possible reducing cholesterol and neutral lipids in the associations between seed size and fatty acid bloodstream and improving circulation At the same composition in diverse genotypes: there were time, DHA is garnering attention as a fatty acid significant correlations between seed size and essential to the brain and other neural tissue. The individual fatty acids: positive with stearic and oleic, fatty acid composition of the fish oils may be and negative with linoleic (Maestri, 1998). different according to species and season.

Table III Cosmetic uses of vegetable oils

Normal skin Almond, apricot, hazelnut, borage, jojoba

Facial care Dry to normal skin Almond, apricot, avocado, olive, wheat germ, borage, jojoba, macadamia

Oily to normal skin Almond, apricot, grapeseed, hazelnut, borage

Normal hair Almond, borage

Hair care Dry hair Almond, avocado, borage, cocoa butter, jojoba, sesame, macadamia

Oily hair Borage, sesame Vol. 51. Fasc. 1-2 (2000) 81

In a recent study (Gámez-Meza, 1999), the fatty oil, noting that emu oil had skin permeability and acid profiles of sardine oils from Sardinops sagax moisturizing properties superior to mineral oil. It has caeruleus of the Gulf of California, were evaluated in been also reported that emu oil increased the three seasonal catch periods. The most abundant proliferation of cells and the growth of hair follicles fatty acids found in the oils were palmitic acid (19.3%), in lab rats. Some of the cosmetic properties of the oleic acid (14.3%), EPA (20.4%) and DHA (12.2%). oil appear to increase synergistically when used in There was no significant difference in the composition combination with phospholipids from other oils used and quality among the six reduction plants where the in cosmetics such as palm, sesame, safflower, samples were obtained. However, a significant borage and coconut. difference in the proportion of EPA and DHA in one of the catch seasons analyzed was observed. In another study, fatty acid composition of the 4.1.1.2. Fats liver oil from the Black Sea dogfish (Squalus Fats are solid at room temperature. They are acanthias) seasonal variations were also usually derived from animals and are complex determined (Stefanov, 1997). mixtures. Fats have a higher percentage saturated fatty acids than do oils. Bird oils Vegetable fats Currently three major species of birds from the Ratite family are being raised in the United States, The fruit and the seeds of diverse vegetable namely the emu, ostrich, and rhea. These birds are species contain fatty fractions of consistency produced primarily for their meat, oil, and leather. The between solid and pasty that are known with the oils obtained from all three species of ratites appear name of vegetable fats. They are mixtures of to be similar in their basic composition. These oils are heterogeneous composition, although they almost triglycerides composed mostly of oleic, palmitic, always present a high content in saturated stearic, and linoleic fatty acids. The proportions of triglycerides. Next, the better known vegetable fats these fatty acids will vary somewhat according to the are indicated. type of bird and possibly the type of feed. Even COCOA OIL: Oil of Theobroma or cacao butter is a though the relationship between animal feed and and yellowish white solid, with an odour resembling that oil compositions has not been studied in depth, it is of cocoa, taste bland and agreeable, generally likely that the degree of saturation of the fatty acids in extracted by expression from the seed of Theobroma the oil will be affected to a certain extent by the type cacao. It has excellent emollient properties and is of fats in the animal feed (Zemtsov, 1996). used to soften and protect chapped hands and lips. The main market for these oils is the cosmetics Applied externally, cocoa butter has emollient virtues. industry. Examples of some commercial products It also presents greasing and lubricating properties. made with ratite oils include moisturizing creams, It is allotted skin conditioning and thickening virtues. body lotions, soap, lip balm and sports ointments. Cocoa butter is thus a good active ingredient EMU OIL: Most of the published data on ratite oils for feel and firmness in lip balms, softening hand is on the emu. Emu are members of the Ratite creams, moisturizing soaps, emollient creams for family of flightless birds, which have small or combination, normal or dry, sensitive and delicate underdeveloped wings. Emu, the world's second skin. It is used as an excipient in ointments and for largest living bird have survived 80 million years in coating tablets and preparing suppositories (del Arco, their native Australia where they are found in the 1997). It has diuretic effect due to stimulation of the deserts, forests and on the plains. In 1960, the emu renal epithelium; it is especially useful when there is was designated Australia's national bird. The main an accumulation of fluid in the body resulting from cosmetic and pharmaceutical properties attributed cardiac failure, when it is often given with digitalis to to this oil are skin penetrating, moisturizing, anti- relieve dilatation. arthritic and anti-inflammatory (Zemtsov, 1996). COCONUT OIL: It is the oil from Cocos nucifera. Work done by Ghosh et al., (1996) reported that Due to its high content in saturated fatty acids emu oil, in combination with ethyl salicylate, (lauric, 50% and myristic, 20%) is an excellent fat isopropyl salicylate, and oil of eucalyptus, has anti- for the synthesis of most of the cosmetic detergents. inflammatory and anti-arthritic activity when tested It is also used in sunscreens (Dave, 1987). It also in laboratory rats with induced polyarthritis. Emu oil contains caprilic and caprinic acids (Pons, 1995). is also reported by these workers to suppress PALM OIL: It is the expressed oil from the fruit of human granulocyte elastase, a tissue degenerative Elaeis guineensis. This oil is also known as vegetable enzyme that is released when tissue inflammation tallow. Because of its high content in unsaturated fatty occurs. Zemtsov et al. reported a double-blind study acids (oleic, 50%; linoleic, 5-10%), may become on the moisturizing and cosmetic properties of emu rancid. They are also present unsaturated fatty acids 82 Grasas y Aceites

(palmitic, > 30% and small amounts of stearic and and biofuel additives. Similar wax esters can also be myristic acids). Unsaponifiable is very scarce, but it produced by microorganisms (del Arco, 1997). contains a relatively high proportion of carotenoids. It JOJOBA OIL: It is a mixture of long chain, linear is used for the production of soaps and, occasionally, liquid wax esters extracted from the seeds of the in products cosmetic dealers. Palm oil adds firmness desert shrub Simmondsia chinensis. Jojoba's liquid to bar soaps and is used in many luxury soaps (Pons, esters provide superior oxidative stability, excellent 1995). emolliency and effective moisturization to the hair SHEA BUTTER: It is also known as african karite and skin (Wisniak, 1977). Human sebum and jojoba butter. It is obtained from the seeds of Butyrospermum oil are virtually identical. Sebum protects and parkii that grows in a wide area in Central Africa. Shea moisturizes the skin and hair, but it is stripped away butter has the aspect of a soft paste or melted fat, with by chemicals, pollutants, the sun, and the aging a greenish, yellowish or whitish colour and a more or process, resulting in dry skin and hair. Jojoba oil less characteristic pleasant odour. Crude shea butter replenishes what skin and hair lose, and it restores has natural antioxidant properties due to its content in them to their natural pH balance. This oil beautifies tocopherols. The content in shea butter of and protects normal skin and hair. Jojoba reduces unsaponifiable fats is remarkable in comparison with wrinkles, treates psoriasis, acne, and neurodermatitis, other oils. This unsaponifiable helps keep the skin and brings the skin back to its normal vitality and young by stimulating the tissue and helping the skin healthy glow. Jojoba oil is similar to, and has make its own collagen. The product is therefore much replaced, sperm whale oil. However, contact appreciated in the cosmetic industry. Shea butter has dermatitis from jojoba oil has been reported (Wantke, soothing, moisturizing and protecting effects. Due to 1996). Used as an additive, jojoba oil improved the the presence of a sizeable quantity of unsaponifiable viscosity index of lubricants. When subjected to fats, its content in vitamins and other active elements, heating and cooling from 40 to 200ºC, the chemical shea butter adds other more precise activities to these structure, kinematic viscosity and refractive index general properties: it has restructuring effects on the remained almost constant. Thus, jojoba oil was highly epidermis, also on dry and fragile hair; it has an anti- stable in this temperature range. elastase characteristic which makes it a good active BEES WAX: It is secreted by the glands of Apis ingredient against stretch marks. Shea butter has also mellifera, acquiring consistency when it mixes with an activity on cell regeneration and capillary the saliva of the bee. This wax has the same sweet circulation. This favours the healing of small wounds, smell as honey and will impart excellent properties skin cracks and crevices, and skin ulcers. In the to body-care products. It is added to bar soaps to cosmetic field, this property is an asset against skin make them harder. It is also used in creams, lotions ageing. It displays a protecting role against UV rays and lip balms (Millet, 1992; del Arco, 1997). Bee because of its content in cinnamic acid and can thus wax is used as an excipient in formulations with the be incorporated in solar products. The latex contained purpose of increasing viscosity and consistency of in shea butter would moreover prevent certain sun the preparations. allergies (Tella, 1979). It is therefore an outstanding SPERMACETI: It is a waxy substance obtained product for cosmetic and pharmaceutical purposes, from the head of the sperm whale (Physeter even incorporated in high proportions. It is easy to macrocephalus). It is mainly constituted by cetyl work into all kinds of emulsions and makes a very palmitate, cetylic alcohol and other esters that good excipient as it prevents allergenic reactions contain fatty alcohols and fatty acids. Spermaceti is without altering the active principles. When added to white, somewhat translucent, slightly unctuous, free soaps it gives an exotic feel. It can also be added to of rancidity. It is one of the solid fatty substances creams and lotions or used alone for massage or skin formerly employed to give consistency and texture cream. to cerates and ointments. For diverse reasons, this The free fatty acid profiles of some vegetable regulator of the consistency of many emulsions is oils and fats are depicted in table IV (Madrid, 1997). being displaced by synthetic esters of similar characteristics (del Arco, 1997). 4.1.2. Waxes LANOLIN: Lanolin is a complex mixture of esters of fatty acids and high molecular weight alcohols, Waxes are esters formed by the combination of including aliphatic or steroid alcohol. Up to 12% fatty acids with high molecular weight monohydroxy consists of free fatty alcohols. It is obtained by alcohols. Waxes minimize water loss on plants and refining the unctuous sebaceous secretion (wool act as waterproofing on animals. In most cases, fat) of sheep. Lipid components from lanolin can be waxes are hard, brittle substances with high melting extracted to use them separately in many points. Liquid wax esters like those from jojoba seed formulations. Lanolin alcohol is extracted by and sperm whale oil are used in diverse commercial hydrolysis of lanolin. It has strong water in oil products as lubricants, cosmetics, solid wax coatings emulsifying properties, absorbing up to 2000 times Vol. 51. Fasc. 1-2 (2000) 83

Table IV Composition (%) of principal oils and fats used in cosmetic and pharmaceutical sciences

Other S.F.A. P.U.F.A. components

Lauric Myristic Palmitic Stearic Palmitoleic Oleic Linoleic Linolenic DHA EPA Oil (12:0) (14:0) (16:0) (18:0) (16:1) (18:1) (18:2) (C18:3)

Almond 4-9 2.5 max 0.6 60-86 7-30 0.1-1.0

Apricot 3-6 2 max 1.4 55-70 25-35 1 max

Avocado 12-20 0.1-2.0 2-10 55-75 9-17 0.1-2.0 Borage 9-12 3-4 15-20 30-40 18-25

Canola 2-7 1-3 50-65 15-30 6-14

Castor

Coffee 30-45 5-9 8-10 40-50 0.1-3

Corn

Cottonseed 17-29 1-3 16-44 33-58 < 2

Grapeseed 5-10 3-5 12-26 58-77

Arachidic (4) Macadamia 7-11 4 max 18-22 55-63 5 max 1 max Eicosenoic (4)

Pumpkin 12.7 6 38 42

Safflower oleic 4-9 2.5 72-80 12-16 0.5max

Safflower linoleic 4-9 2.5 75-80 12-16 0.5max

Soybean 7-12 2-6 20-35 45-60 5-10

Sunflower 3.5-8 3-7 15-85 50-72 < 0.2

Sesame 7-12 3.5-6 0.5 35-50 35-50 1 max

β-sitosterol Tomato 14 6 22 54 cholesterol

Walnut 6-9 2-3 15-20 57 62 11-14

Wheatgerm 9-17 1-3 22-40 45-65 1

Cocoa 25-30 31-35 34-36 3

Coconut 50 20 16 3 4

Palm 30 50 5-10

Peanut 8-13 3-5 38-63 18-42

Shea butter 6 38 49 4

its own weight, and is used as a binder, emulsion soluble in mineral oil, making it useful in bath oil stabilizer, skin conditioner, hair conditioner and products. The other component of fractionation is viscosity-increasing agent in products such as lanolin wax. This substance is also odorless and lipsticks, make-up, eye products and creams and tasteless, and is a better water in oil emulsifier than lotions. Liquid lanolin is obtained by solvent plain lanolin. It is used primarily in lispsticks and fractionation of lanolin. It is odorless, tasteless and glosses. Hydrogenated lanolin is a more saturated 84 Grasas y Aceites

derivative with a large percentage of free alcohols. arteriosclerosis and many people are trying to It has increased water absorption and mineral oil reduce the amount of fatty acids in their diet (Fan, solubility, is odorless and tasteless, and is used in 1998; Truswell, 1998). lip products, scented moisturizing ad night creams Fatty acids derivates (fatty acid soaps, simple and lotions, cleansing products and emulsion fatty acid ester, modified fatty acid ester and fatty formulas. Acetylated lanolin is a more hydrophobic alcohol ether) are used as emulsifiers in many product with a high ester and low alcohol content. It foods, cosmetical and pharmaceutical preparations is useful in water-resistant products such as (del Arco, 1997). sunscreens, baby products, and hand and body If the free bonds in a fatty acid chain of carbon creams (del Arco, 1997). Ethoxylated lanolins, also atoms are not all occupied by hydrogen atoms, the known as polyoxyethylene lanolins, are reacted with fatty acid is said to be unsaturated. Oils consisting ethylene oxide, resulting in a more hydrophilic mainly of the glycerides of unsaturated fatty acids product containing 6 to 75 mol of ethylene oxide. are generally liquid at normal temperatures. They They are used as solubilizers in sunscreens, may be made more solid by hydrogenation which perfumes, pharmaceuticals, hair products, shampoos, reduces the degree of unsaturation. Fatty acids soaps, dishwashing detergents, aftershave lotions, containing only one unsaturated bond are called preshave lotions, astringent lotions and colognes. «monounsaturated»; those with more than one Transesterified lanolin is partially saponified and is unsaturated bond are called «polyunsaturated». more soluble and spreadable than lanolin. It is used OLEIC ACID (18:1): It is employed in cosmetical to create a lighter velvety-feeling emulsion in and pharmaceutical formulations as an excipient. It nongreasy formulations (Smolinske, 1992). On the is used in topical and parenteral pharmaceutical other hand, several puzzling aspects of the use of formulations. It has also been used as penetration lanolin are discussed by Wolf (1996). In this paper, enhancer in transdermal formulations (Morgan, it has been reported that lanolin in topical 1998), to improve the bioavailability of poorly-water therapeutic agents sensitizes a high proportion of soluble drugs in tablet formulations, and as raw patients, whereas the same lanolin is 'safe' in material for ointments, creams, etc. cosmetics so widely used by millions of individuals. LINOLEIC (18:2) AND LINOLENIC (18:3) ACIDS are used in cosmetic products. They influence on metabolic processes in the skin, promote the activity of vitamins 4.2. Fatty acids A and E and recovery barrier properties of stratum corneum (Belotserkovets, 1998; Huang, 1999). The combination of fatty acids with glycerol to form glycerides is sometimes reversed resulting in the presence of uncombined or free fatty acids. 4.3. Compound lipids These are usually found in crude oils and may be removed by neutralisation. 4.3.1. Phospholipids Fatty acids are long molecules consisting of a hydrocarbon chain with a carboxylic acid group at the Phospholipids are amphipatic molecules. The end. The long tail of the molecule, made up of carbon head of a lipid molecule is negatively charged and hydrogen, is not attracted to water. The phosphate group and the two tails are highly carboxylic acid «head» can form hydrogen bonds hydrophobic hydrocarbon chains. Phospholipid tails with water, and is therefore strongly attracted to will congregate together to form a local hydrophobic water. When a fatty acid is placed on a water surface, environment. This leaves the charged phosphate the hydrophilic heads of the molecules are attracted groups facing out into the hydrophilic environment. to the water. As a result, the molecules form a There are three structures that phospholipids can monolayer on the surface of the water with their form because of their amphipatic nature: micelles (A), heads sticking into the water and their hydrophobic planar lipid bilayers (B) and vesicles (C) (Figure 1). tails sticking up above the surface of the water. A phospholipid bilayer is approximately 5 nm Although fatty acids are relatively large thick. This membrane is semipermeable, meaning molecules, they are not biopolymers made up of that most molecules are excluded but some consecutive units like carbohydrates and proteins. molecules are allowed to pass freely through the Fatty acids, as a group, are a member of the membrane. larger class of ubiquitous lipids, which carry out A broad range of phospholipids are suitable for numerous biochemical functions ranging from use in cosmetics, pharmaceuticals and diagnostics. construction of cellular membranes to providing Phospholipids are used as a vehicle for therapeutic food under starvation conditions. substances. They are also used for preparing Recently, fatty acids have come under heavy liposomes. Liposomes are small vesicles formed by scrutiny for their role in heart disease and a membrane bilayer of phospholipids which contain Vol. 51. Fasc. 1-2 (2000) 85

stabilize components such as N-(1-(2,3- dioleoyloxy)propyl)-N,N, N-trimethylammonium chloride (DOTAP) and DOPE in the membrane bilayer. DOTAP, a cationic lipid, is incorporated into these formulations to promote «passive» binding of AB Cliposomes to target cells (which bear a net negative charge), whereas DOPE is included as a Figure 1 «fusogenic» lipid. The presence of the pegylated Structures that lipids can form ceramide has been shown to inhibit fusion between liposomes as well as between liposomes and cells. Synthetic phospholipids are suitable for specific different substances of pharmaceutical or cosmetic applications in liposome targeting and gene therapy interest (Ostro, 1989). (Hodgson, 1996; Li, 1998). Liposomal encapsulation or incorporation in a Gene therapy delivery is attempting a solution lipid complex can substantially affect a drug's for the efficient delivery of genes to their intended functional properties relative to those of the targets. Researchers have successfully put DNA unencapsulated or nonlipid-associated drug. In into liposomes and have achieved fusion of these addition, different liposomal or lipid-complexed liposomes to cells, thereby accomplishing the direct products with a common active ingredient may vary delivery of the liposome contents into the cell from one another in the chemical composition and interior. Scientists have also succeeded in physical form of the lipid component. Such protecting these liposomes from degradation and differences may affect functional properties of these are able to modulate their circulation time. drug products (Ostro, 1992). Researchers are now developing systems to target Lipid-complexes products are a therapeutic these fusogenic liposomes to particular cell types option to decrease toxicity of some drugs, such as (Balasubramaniam, 1996; Zuidan, 1999). Amphotericin B (Janoff, 1993). It is also possible to find in the bibliography Conventional amphotericin B has been generally liposomes made with different types of considered the drug of choice for many types of phospholipids: distearoylphosphatidylcholine (Ahl, systemic fungal infections. These infections are a 1997), dipalmitoylphosphatidylcholine (Jones, 1997; major threat to those whose immune systems are Asai, 1999), etc. compromised, such as patients undergoing chemotherapy for cancer, bone marrow transplant 4.3.1.1. Lecithin recipients and AIDS patients. However, Lecithin is a lipid complex compound of glycerol amphotericin B is very toxic, thus limiting its utility. containing phosphorus. It has two fatty acid radicals For these patients, who have a high rate of and a third radical which is a complex organic base morbidity and mortality, there is a dosage form containing both phosphorus and nitrogen. It has distinct from conventional amphotericin B, which strong emulsifying properties and is also used in consists of amphotericin B complexed with two food industry, pharmaceuticals and cosmetics phospholipids in approximately a 1:1 drug-to-lipid (Smolinske, 1992; Helme, 1992). molar ratio: L-a-dimyristoylphosphatidylcholine Lecithins are an important structural component (DMPC) and L-a-dimyristoylphosphatidylglycerol of the cell membrane, where it maintains continuity (DMPG), present in a 7:3 molar ratio (Fromtling, between the water and lipids phases inside and 1996; Hiemenz, 1996; Baddour, 1997). Clinical outside the cell. experience demonstrates that the complexing of It is commonly used as an emulsifying agent and amphotericin B with these phospholipids reduces skin conditioner. Types of products include commonly observed toxicities of amphotericin B, shampoos, make-up foundations, blushes, lipsticks, particularly those affecting the kidney (Dix, 1996). and moisturizing creams or lotions. The usage of Liposomal doxorubicin is designed to target to lecithin considerably increases quality of cosmetic tumor cells and spare healthy tissue, maintaining products (nutritius, rejuvenation, regenerating efficacy while reducing toxicity. Conventional functions), and considerably improves its doxorubicin, drug commonly used to treat cancer, is organoleptic parameters without significant rise in limited by its potential for causing a variety of severe price (Kusmina, 1998). side effects, particularly irreversible heart damage (Batist, 1998). Programmed Fusogenic Liposomes (PFV) are designed to deliver bioactive compounds 4.3.2. Sphingolipids to the cytoplasm of cells by fusing with cell membranes in a controlled, regulated manner. PFV Sphingolipids are compound lipids that contain a contain a pegylated-ceramide which acts to sphingoid group. 86 Grasas y Aceites

4.3.2.1. Ceramides an ingredient in some pharmaceutical preparations as liposomes. Ceramides are sphingolipids that contain an Sterols are also required for the growth of most N-acetylated sphingoid. They are skincare cosmetic fungi. It has been established that the more ingredients for regulating transepidermal water loss primitive taxa of fungi have cholesterol and related and promoting epidermal barrier repair. sterols while the more advanced taxa have The main barrier function of a skin belongs to the ergosterol as the major sterol (Parks, 1998). multilamellar lipid sheets of the stratum corneum. These lipids are formed in the deeper layers of epidermis, and then lose their polar heads under the action lipolytic enzymes on its way to a surface. Thus, 5. LIPIDS AS ACTIVE SUBSTANCES IN lamellar structures cementing cells of epidermis are PHARMACEUTICALS formed from fatty acids, acylglycerols and ceramides. In a growing old skin, under influence of external Up to now, the most important lipids used in the environment, including agents for clearing skin, pharmaceutical and cosmetic Industry as lipids leave the stratum corneum, making epidermis exicipients in medicines and cosmetics has been more permeable. It results in deterioration of barrier described. Next, it will be carried out a study of function of skin and increasing of water loss. lipids, in function of their biological activity, as active Therefore, application of «substituting therapy» by substances for the elaboration of pharmaceuticals, inclusion in cosmetic agents ceramides and other cosmetics or nutritional supplements. normal components of a lipid barrier is a simple and effective way of reconstruction of skin barrier function. Ceramides are combined with epidermis 5.1. Triglycerides growth stimulators such as alfa-hydroxiacids and retinoids (Moureaux, 1995). Triglycerides are the chemical form in which Hair also loses lipids. With increasing age, the lipids exist in food as well as in the body. In plasma perceptible characteristics of the hair are altered. In they are derived from fats eaten in foods or made in healthy hair, the edges of the cuticle cells are the body from other energy sources like smooth and the patterns of the cuticle are regular. In carbohydrates. Calories ingested in a meal and not damaged hair, the cuticle edge is missing and in used immediately by tissues are converted to some parts, the scale lifting and loss progresses to triglycerides and transported to fat cells to be underlying layers. When the damage has progressed stored. Hormones regulate the release of further, the cuticle is almost completely missing and triglycerides from fat tissue so they meet the body's the cortex is exposed. The result of the needs for energy between meals. accumulated damage is limp, dull, split and broken hair. This weakened hair, now with a dramatically 5.1.1. Vegetable oils lowered tensile strength, is then chronically exposed to chemicals, harsh surfactants, U.V. radiation and BORAGE OIL: Contains 20-24% gamma-linolenic mechanical and physical constraints imposed on acid (GLA), a non-essential fatty acid, which has the hair. Ceramides applied on this biologically dead been shown to have many beneficial effects. It has structure, exhibit new ways in which subtle the highest GLA content of any plant source. modifications may provide care and protection of Studies show borage oil to be beneficial in the the hair fiber (Kaplun, 1998). treatment of rheumatoid arthritis, atopic eczema and diabetic neuropathy, as well as in the reduction 4.3.2.2. Sphingosines of cholesterol levels (Barre, 1992; Mancuso, 1997; Henz, 1999). Phytosphingosine and tetraacetylphytosphingosine CANOLA OIL: It is the oil from canola, a genetic are used for rejuvenation of skin. It have variation of rapeseed developed by Canadian plant antimicrobial and antiinflamatory effects. breeders specifically for its nutritional qualities, particularly its low level of saturated fat. The fatty 4.4. Derived lipids acid composition of canola oil is consistent with its use as a substitute for SFA, in meeting the dietary 4.4.1. Steroids goals recommended by many health associations. Canola oil is a newly marketed edible vegetable oil The steroids are chiefly hormones, including for use in salads and for cooking that contains 55% estrogen and testosterone. Cholesterol is an steroid of oleic acid, 25% linoleic acid and 10% that is component of the cell membrane, and an alpha-linolenate and only 4% of the saturated fatty important factor in the disease atherosclerosis acids that have been implicated as factors in (Kruth, 1997; Bocan, 1998). Cholesterol is used as hypercholesterolemia (Dupont, 1989). Health Vol. 51. Fasc. 1-2 (2000) 87

practitioners and dieticians have praised the fatty disease, in Greenlandic Eskimos is extremely low. acid profile of canola, labelling it the oil with the best From 1963 to 1967 only three cases of these diseases fatty acid ratio. Research indicates the fatty acid were reported in the entire Eskimo population of composition of canola oil is most favourable in Greenland. terms of health benefits and as part of a nutritionally Since diabetes and heart disease affected balanced diet. literally millions of Americans in the 1980's and EVENING PRIMROSE OIL: Is extracted from the 1990's, the lack of heart disease in Eskimos and seeds of Oenothera biennis (Onagraceae), a plant other societies has attracted the serious attention of native to North America and which is now widely many scientists around the world. Low mortality cultivated in temperate countries. This oil has a high from coronary heart disease among Eskimos has content of glycerides of linoleic acid (65-80%) and been attributed to less atherosclerosis in the gamma-linolenic acid (7-14%). Because of this high coronary arteries because of a high dietary intake of gamma-linolenic acid content, evening primrose oil omega-3 fatty acids (Newman, 1993). is widely used as a dietary supplement, providing The food of the Greenlandic Eskimos consists additional quantities of this essential fatty acid largely of meat from whales, seals, sea birds and fish (Dewick, 1997). It has been suggested that the (usually halibut and salmon). Needless to say, their alpha-linolenic acid contained in perilla oil is less food is extremely rich in protein and fat and low in atherogenic than oleic and linoleic acid, and carbohydrates, but it is extremely high in the omega-3 gamma-linolenic acid contained in evening polyunsaturates EPA and DHA (Harris, 1999). [corrected] primrose oil has a tendency to decrease In many studies there is evidence that high the plasma lipid level. (Sadi, 1996). levels of EPA and DHA found in the fish, seal and OLIVE OIL: Significantly increased the plasma HDL whale diet of the Eskimo may be protective against cholesterol concentration, but only decreased the heart disease (Ponte, 1997). plasma LDL cholesterol concentration in healthy SHARK LIVER OIL is obtained from the liver taken from subjects (Ruiz-Gutiérrez, 1998). Moreover, olive oil deep sea sharks. Scandinavian fishermen have been was able to significantly diminish the systolic and using shark liver oil since the 16th century. It is used to diastolic blood pressures in hypertensive patients combat viral infections such as colds and influenza as (Muriana, 1998). Olive oil enriched-diet may an antiseptic to heal wounds. It has composed of 60% modulate and/or partially prevent the alteration of unsaponifiable matter, containing 45% squalene, 5% those pathogenic parameters related to human cholesterol and 10% of linear saturated and hypertension and cardiovascular pathology, monounsaturated glycerol ethers with 14 - 18 carbon although these processes cannot be exclusively atoms (Bordier, 1996). The active ingredients in shark ascribed to the content of oleic acid in virgin olive liver oil have found to be a group of ether-linked oil. The fraction of sterols and triterpenic dialcohols glycerols known as alkylglycerols. They are special from the unsaponifiable of virgin olive oil has been marine lipids that support the production of white blood tested for its possible anti-inflammatory activity. The cells, particularly the T-Lymphocytes which are critical topical administration of these products a potent to the proper function of the immune system. The anti-edematous effect, in the auricular edema immune supportive nutritional effect of alkoxyglycerols induced by TPA (12-O-tetradecanoylphorbol acetate) helps the body protect against all three types of in experimental animals (de la Puerta, 1997). In other common offenders including bacterial, fungal and viral study, it has been reported that virgin olive oil infections. These natural immune supporting nutrients succesfully protects mitochondrial membranes from also help the immune system fulfill its role of warding aged rats against the free radical insult (Huertas, 1999). off the progression of other degenerative conditions: AIDS, cancer, auto-immune disorders and allergic 5.1.2. Fish oils reactions (Pugliese, 1998).

The relationship between fish oils and 5.1.3. Fats atherosclerosis appears to be an intimate one. The higher the consumption of fish, the lower the risk of SHEA BUTTER can be used to treat rheumatism dying from coronary heart disease. In people with and aching muscles, and to ease colds because it coronary heart disease, fish oils may reduce the risk decongests nasal mucous tissues (Tella, 1979). of thrombosis, reduce the pain of angina and improve cardiac function. There is even preliminary evidence that they may inhibit the development of 5.2. Fatty acids atherosclerosis. According to studies published in Lancet Fatty acids have an important role to prevent (Anonymous, 1986), the incidence of heart disease cardiovascular diseases. SFA are the main dietary related to atherosclerosis, including coronary artery culprit in raising blood cholesterol. Diets high in SFA 88 Grasas y Aceites

and trans fatty acids increase LDL cholesterol To reduce serum levels of total cholesterol and levels, and in turn, the risk of heart disease. low-density lipoprotein cholesterol, without reducing (Lichtenstein, 1998). The main sources of SFA in caloric intake, it may be beneficial to substitute the the diet are foods from animals (beef, veal, lamb, whole milk customarily consumed by children with a pork, butter, cream, milk and cheeses) and some milk preparation of fat-free milk enriched with oleic plants (coconut oil, palm oil and cocoa butter). acid (Estévez-González, 1998). UFA tend to help the body get rid of newly formed cholesterol. Thus, they keep the blood cholesterol 5.2.3. Polyunsaturated fatty acids level down and reduce cholesterol deposits in artery walls (Poschl, 1999). Monounsaturated oils are liquid Numerous studies have shown that these fatty at room temperature but start to solidify at acids help lower cholesterol and blood triglycerides, refrigerator temperatures. Olive and peanut oils and and help prevent clots in arteries which may result avocados are sources of monounsaturated fatty in strokes, heart attacks and thromboses (Ponte, acids. Polyunsaturated oils are liquid. They easily 1997). combine with oxygen in the air to become rancid. LINOLEIC and α-LINOLEIC are referred to as Common sources of polyunsaturated fatty acids are essential fatty acids since they and their metabolites safflower, sesame and sunflower seeds, corn and are required for normal good health. Some food soybeans, many nuts and seeds, and their oils. sources such as the oils present in fish are rich in the later metabolites derived from α-linolenic acid 5.2.1. Saturated fatty acids (EPA and DHA), and are also beneficial to health. Since these fatty acids all have a double bond three CAPRYLIC ACID is an antifungal, short chain, fatty carbons from the methyl end of the chain, they are acid having the chemical name octanoic acid. grouped together under the term ω-3 fatty acids. Caprylic acid is a fatty acid derived from coconut oil Although most plant-derived oils contain high and has been found to exhibit antifungal properties. It amounts of unsaturated fatty acid glycerides, specifically is effective for gastrointestinal Candida including those of linoleic and α-linoleic acids, the overgrowth. Once absorbed, caprylic acid is no longer conversion of linoleic into γ-linolenic can be blocked antifungal but is then metabolized to produce energy. or inhibited in certain conditions in humans. This The antifungal effect of caprylic acid has been restricts synthesis of prostaglandins. In such cases, demonstrated in both clinical and in vitro studies. In the use of food supplements (evening primrose), the pH range of 2.5-8.5, caprylic acid exhibits high which are rich in γ-linolenic esters, can be valuable fungicidal activity against yeasts, especially and help in the disorder. Candida albicans. The exact mechanism of ARACHIDONIC ACID itself has not been found in fungicidal action is not fully understood; however, it higher plants, but does occur in some algae, mosses is postulated that caprylic acid dissolves in the cell and ferns. Arachidonic acid is a precursor of the membrane of yeast causing changes in fluidity and prostaglandins, thromboxanes and leukotrienes, permeability that lead to membrane disaggregation. which show a range of pharmaceutical activities and Caprylic acid is readily absorbed in the also stimulates protein kinase redistribution in heart intestines; however, sustained release dosage cells (Kim, 1992; Blobe, 1995; Huang, 1997). forms allow for a slow, uniform dispersion along the Lipoxins are arachidonic acid-derivatives intestinal length ensuring delivery of caprylic acid to products. They were first isolated in 1984 and play the colonic region where Candida infestation is critical roles in inflammation and other multicellular usually maximal. It has been said that Candida vascular processes, including atherosclerosis and migrate into the mucosal wall. Because of its thrombosis (Serhan, 1997). lipotrophic properties (which allow it to penetrate Animals need linoleic for the biosynthesis of mucosal cells) caprylic acid is also believed to be dihomo-γ-linolenic and arachidonic, polyunsaturated effective against intramucosal Candida. Absorbed fatty acid precursors of prostaglandins in the «one» caprylic acid can be oxidized both in the and «two» series respectively. Linoleic acid must be mitochondrial and extra-mitochondrial compartments obtained from plant material in the diet, and then of mammalian tissues thereby eliminating additional desaturated near the carboxyl end to yield toxic burden to the liver. γ-linolenic, which is then used as the substrate for further chain extension, producing dihomo-γ- 5.2.2. Monounsaturated fatty acids linolenic. Arachidonic derives from this additional desaturation, again towards the carboxyl end of the OLEIC ACID has been shown to reduce serum chain. α-linolenic is similarly a precursor on the way levels of total cholesterol and LDL cholesterol to EPA, required for the synthesis of prostaglandins levels. Oleic acid does not affect levels of HDL of the three series, and it is also obtained from the cholesterol. diet (Dewick, 1997). Vol. 51. Fasc. 1-2 (2000) 89

Polyunsaturated fatty acids (linoleic acid, linolenic body cells, membranes are the main working surfaces. acid, arachidonic acid and DHA) but neither the PLs (phosphatidylserine, phosphatidylcholine, monounsaturated oleic acid nor the saturated stearic phosphatidylethanolamine and phophatidylinositol, acid), reduce membrane electrical excitability in etc.) promote membrane fluidity which is crucial for neonatal rat cardiac myocytes. These results show cellular responsiveness and for processing of that free polyunsaturated fatty acids can reduce nutrients and information by the cell. membrane electrical excitability of heart cells and With age, the membranes tend to get stiffer and provide an electrophysiological basis for the more resistant to the normal movement of molecules. antiarrhytmic effects of these fatty acids (Kang, 1995). Less movement of molecules means decreased EICOSAPENTAENOIC ACID is the precursor to the function in brain cells. PLs relax membranes, series 3 prostaglandins (PGE 3) and also provides allowing for more normal function. a natural approach to lower blood cholesterol and Nerve cells especially depend on membranes to triglycerides. Prostaglandin E3 is directly carry out their specialized functions. For example, responsible for making blood platelets less sticky, membranes in nerve cells generate the electrical thus leading to an easier flow of blood throughout current of a thought, transmit that current along the our bodies. This natural antithrombotic «anti- cell's axon and relay the current from cell to cell. In clotting» effect of EPA has been well researched. all of these processes, membrane proteins play key This means that EPA is intimately involved in bodily roles, and PLs regulate the activities of such processes that inhibit blood clots, particularly in the proteins. PLs not only aid in the conduction of nerve small capillaries of the heart (Stefanov, 1997). impulses, they also help accumulate, store and DOCOSAHEXAENOIC ACID, an omega-3 long chain release nerve transmitter substances, supporting polyunsaturated fatty acid, is the building block of homeostasis in the brain. human brain tissue. It is the primary structural fatty PLs may be usefull in the age-related decline in acid in the gray matter of the brain and retina of the memory and concentration, epilepsy, Parkinson's eye. Brain tissue is about 60% lipid (structural fat, disease and Alzheimer's disease. not adipose fat) and about 25% of that is DHA. LECITHIN is the chief phospholipid found in bile and Humans obtain DHA from their diets, initially is important in keeping the bile in solution and not through the placenta and from breast milk. DHA is precipitated out in the form of gallstones. It may also essential for brain and eye development and for aid in removing cholesterol from arterial walls and mental and visual function. Fish provide a rich source increase immunity against viral infections. Lecithin of DHA but like humans, fish do not adequately plays an important part in maintaining a healthy synthesize it and obtain DHA from microalgae. nervous system and is found naturally in the myelin An expert panel of the World Health Organization sheath, a fatty protective covering for the nerves. It is has recommended that all infant formula be high in phosphorus and unites with iron, iodine and enriched with this fatty acid. DHA is the most calcium to give power and vigor to the brain. abundant omega-3 long-chain polyunsaturated fatty A particularly important natural phospholipid is acid found in breast-milk. Several studies on the PLATELET-ACTIVATING FACTOR (PAF), which resembles a development of intelligence in both term and phosphatidylcholine. It activates blood platelets and pre-term infants indicate that when all recognized contributes to diverse biological effects, including confounding factors (e.g., parental age, IQ, thrombosis, inflammatory reactions and allergies socioeconomic class, child's birth weight, etc.) are (Dewich, 1997). accounted for, the children (18 months to 15 years) Lysophosphatidic acid (LPA), formed during mild who were breast-fed had a significantly higher oxidation of LDL, is an atherothrombogenic molecule, IQ - 2 to 9 points - compared to formula-fed infants. initiating platelet activation and stimulating The brains of Alzheimer's patients show lower endothelial cell stress-fiber and gap formation levels of DHA and of arachidonic acid than do the (Siess, 1999). brains of healthy geriatric patients and epidemiological research shows a correlation between reduced intake of this fatty acid and the 5.4. Sphingolipids increased incidence of depression and dementia. DHA also inhibits the effect of dihydropyridine The «sphingosine» backbone of sphingolipids (DHP) agonists and antagonists on Ca2+ channels was so named by J.L. Thudichum in 1884 for its (Pepe, 1994). enigmatic («Sphinx-like») properties. Research on the involvement of sphingolipids in the signal 5.3. Phospholipids transduction pathway that mediate cell grown, differentiation, multiple cell functions, and cell death Phospholipids (PLs) are important structural has been rapidly expanding our understanding of components of cell membranes. Of all brain and these compounds (Merrill, 1997). 90 Grasas y Aceites

The sphingolipid cycle encompasses a large independent of the cyclooxygenase enzyme (Rokach, family of biomolecules which play unique and diverse 1998). Since these compounds are isomeric to roles in signal transduction. In a process analogous prostaglandin F2 formed by the cyclooxygenase, they to the phospholipase C- mediated production of have been termed F2-isoprostanes (Roberts, 1999; diacylglycerols, sphingomyelinase hydrolyzes Morrows, 1999). sphingomyelin producing ceramide, a second messenger which can stimulate protein phosphatase 5.6. FAT-OIL VITAMINS 2A, MAP kinase and induce apoptosis. Ceramide is a potent biomolecule with effects in 5.6.1. Carotenoids multiple cell signaling pathways. Increases in cellular ceramide levels may lead to cell growth Carotenoids are red, yellow and orange arrest, cell differentiation or programmed cell death pigments which are widely distributed in nature. (apoptosis) (Dobrowsky, 1998). They contain a conjugated backbone composed Ceramide may be converted, via ceramidase, to of isoprene units, which are usually inverted at the sphingosine, which displays a variety of activities, or center of the molecule, imparting symmetry. Changes phosphorylated to ceramide 1-phosphate. Sphingosine in geometrical configuration about the double bonds can be converted to sphingosine-1-phosphate result in the existence of many cis and trans which is mitogenic and stimulates calcium release isomers (O'Neil, 1992). from intracellular stores. Inducers of sphingomyelin Carotenoids absorb light in the 400-500 nm breakdown and release of sphingoid second region of the visible spectrum. This physical messengers include TNF-α, γ-interferon, IL-1, property imparts the characteristic red/yellow color 1α,25-dihydroxyvitamin D3, complement components of the pigments. and diverse forms of cellular stress (Brown, 1998). Although specific carotenoids have been Ceramides and sphingosines are molecules identified in photosynthetic centers in plants, bird widely implicated in cell differentiation and apoptosis. feathers, crustaceans and marigold petals, they are In vitro, they have been shown to be active against especially abundant in yellow-orange fruits and several human cancers including non-small-cell lung, vegetables and dark green, leafy vegetables breast, renal cell, ovarian and colon cancer, as well (Beecher, 1992). Of the more than 700 naturally as against drug resistant cell lines (Merrill, 1997). occurring carotenoids identified thus far, as many as Nichols (1998) has recently reported that 50 may be absorbed and metabolized by the human Porphyromonas gingivalis synthesizes at least four body. To date, only 14 carotenoids have been major ceramides and two of these are selectively identified in human serum. adsorbed to diseased tooth surfaces and may The established efficacy of beta-carotene in penetrate into diseased gingival tissue. quenching singlet oxygen and intercepting deleterious free radicals and reactive oxygen 5.5. Prostaglandins species makes it part of the diverse antioxidant defense system in humans (Ozhogina, 1995). The prostaglandins are a group modified C20 Reactive oxygen species have been implicated in fatty acids first isolated from human semen and the development of many diseases, including initially assumed to be secreted by the prostate ischemic heart disease, various cancers, cataracts gland. They are now known to occur widely in and macular degeneration (Halliwell, 1992). In vitro animal tissues, but only in tiny amounts. experiments have also demonstrated that lycopene, Prostaglandins are biosynthesized from three alpha-carotene, zeaxanthin, lutein and cryptoxanthin essential fatty acids: dihomo-gamma-linolenic quench singlet oxygen and inhibit lipid peroxidation acid, arachidonic acid and eicosapentaenoic acid, (Di Mascio, 1989). which yield prostaglandins of the 1-, 2- and 3-series, Carotenoids are absorbed from the intestine with respectively. the aid of dietary fat and incorporated into They have been found to exert a wide variety of chylomicrons for transport in the serum. Due to the pharmacological effects on humans and animals. hydrophobic character, carotenoids are associated They are active at very low, hormone-like with lipid portions of human tissues, cells and concentrations and can regulate blood pressure, membranes. The major serum carotenoids are gastric secretions, platelet aggregation and beta-carotene, alpha-carotene, lutein, zeaxanthin, contractions of smooth muscle. (Dewick, 1997; lycopene and cryptoxanthin. Smaller amounts of Groenewald, 1997). polyenes such as phytoene and phytofluene are also Isoprostanes: In 1990, it has been reported the present. discovery that prostaglandin (PG) F2-like compounds BETA-CAROTENE: the all-trans isomer of this are formed in abundance in vivo by free radical carotenoid is the major source of dietary retinoids, catalyzed peroxidation of arachidonic acid, due to its high provitamin A activity (Wang, 1998). Vol. 51. Fasc. 1-2 (2000) 91

Beta-carotene quenches singlet oxygen, induces Retinoids and their analogues have been evaluated gap junction communication and inhibits lipid as chemoprevention agents, and also in the peroxidation (Zhang, 1991). High serum levels of management of acute promyelocytic leukaemia beta-carotene are correlated with low incidences of (Wiegand, 1998; Evans, 1999). cancer in the mouth (Stich, 1991), lung (Stahelin, The synthetic retinoic acids tretinoin (retinoic acid) 1991), breast (Wald, 1984), cervix (Palan, 1991), and isotretinoin (13-cis-retinoic acid) are retinoids skin (Ramaswamy, 1990) and stomach (Stahelin, that are used as topical or oral teatments for acne 1991). Beta-caroteno is used for protecting lungs vulgaris, reducing levels of dehydroretinol and from air pollutants and as lung protection for modifying skin keratinization. Dehydroretinol levels in smokers and ex-smokers. the skin become markedly elevated in conditions ALPHA-CAROTENE: this carotenoid is similar to such as eczema and psoriasis (Griffiths, 1999). beta-carotene in its biological activity, but quenches singlet oxygen more effectively (Di Mascio, 1989). 5.6.3. Tocopherols Alpha-carotene improves gap junction communication, prevents lipid peroxidation and inhibits the Vitamin E designates the group of compounds formation and uptake of carcinogens in the body (tocol and tocotrienol derivates) which exhibit (Zhang, 1991). High serum levels have been qualitatively the biological activity of α-tocopherol. It associated with lower risks of lung cancer. With one is an essential nutrient which must be supplied in half the provitamin A potency of beta-carotene, the diet. Affortunately, vitamin E is widespread in alpha-carotene also restores normal cell growth and our food supply and is found mainly in vegetable oils differentiation. (such as canola, sunflower, safflower, olive and LUTEIN: this xanthophyll exists in the retina. It wheat germ oil), nuts, whole grains and egg yolks. functions to protect photoreceptor cells from light- Smaller amounts are found in fruits, vegetables, generated oxygen radicals, and thus plays a key role meats and fish. in preventing advanced macular degeneration Vitamin E is present in all cell membranes, (Schalch, 1992). Lutein does not possess provitamin plasma lipoproteins and red blood cells. As the A activity. Zeaxanthin: in addition to lutein, zeaxanthin major lipid-soluble chain-breaking antioxidant in exists in the retina and confers protection against humans, it functions to protect DNA, LDL and macular degeneration (Schalch, 1992). Zeaxanthin is PUFAs from free radical-induced oxidation. Vitamin also prevalent in ovaries and adipocyte tissue E also quenches singlet oxygen. In this regard, (Kaplan, 1990) This xanthophyll does not possess d-alpha-tocopherol is the most biologically active provitamin A activity. Lutein and zeaxanthin may have isomer (Sies, 1992). protective effects against LDL oxidation (Forman, Approximately 40% of ingested vitamin E is 1995). absorbed Long chain dietary triglycerides enhance Many epidemiological studies have established absorption. The different isomers are also absorbed an inverse correlation between dietary intake of with different efficiency. Vitamin E and fish oil yellow-orange fruit and dark green, leafy vegetables potentiated the effect of each other (Chen, 1999). and the incidence of various cancers, especially Iron supplements destroy vitamin E. High those of the mouth, pharynx, larynx, esophagus, intakes of vitamin A reduce the uptake of vitamin E, lung, stomach, cervix and bladder (Ziegler, 1991; whereas high doses of vitamin E can impair the Block, 1992). absorption of vitamin K. The recent attention given to the possible role of 5.6.2. Retinoids vitamine E and carotenoids in the prevention and treatment of a variety of illnesses resulted in Vitamin A and its biologically active derivatives, segments of the population increasing their retinal and retinoic acid, together with a large consumption of these antioxidants. Once repertoire of synthetic analogues are collectively consumed, vitamine E and carotenoids are thought referred to as retinoids. Vitamin A1 (retinol) and vitamin to follow the same absorptive pathway and may A2 (dehydroretinol) are fat-soluble vitaminsfound only influence each other's absorption, particularly when in animal products, especially dairy products, eggs and taken in large doses. These results suggest that animal livers and kidneys. Fish liver oils (halibut-liver concurrent consumption of a large dose of vitamine oil and cod-liver oil) are particularly rich sources. They E may influence carotenoid bioavailability exist as free alcohols or as esters with acetic and (Hageman, 1999). palmitic acid (Dewick, 1997). Inverse correlations between serum levels of Naturally occurring retinoids regulate the growth vitamin E and the incidence of diseases such as and differentiation of a wide variety of cell types and arthritis, cancer, cataracts and advanced macular play a crucial role in the physiology of vision and as degeneration have been established. The risk of morphogenic agents during embryonic development. developing coronary diseases such as ischemic heart 92 Grasas y Aceites

disease (Gey et al., 1991), atherosclerosis and West-Coast Eskimos. By H.O. Bang, J. Dyerberg, Aase angina pectoris (Riemersma et al., 1991) was shown Brondum Nielsen. Nutr. Rev. 44, 143-146. to be dramatically reduced in individuals with a high Arco, J. del, Arruza, M.A., Diego, M. de, Fuertes, A., vitamin E status. In vitro data suggest that vitamin E Garmendía, G., González, M., Ibañez, D., Melero, R., Monje, I., Ordieres, E., Torre, M.A. and Urruticoechea, protects against oxidation of low-density lipoproteins A. (1997) Formulación Magistral de Medicamentos, 4ª and decreases the deposition of atherogenic oxidized ed., Ed. Colegio Oficial de Farmacéuticos de Vizcaya, low-density lipoprotein in arterial walls (Spencer, Bilbao. 1999). Moreover, the ability to of vitamin E and its Asai, Y. and Watanabe, S. 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