Fish oils, shark cartilage, shark liver oil and fat-soluble vitamins have been on the market since the beginning of the 20th century. An increasing understanding of the properties of lipid nutritional supplements allows for better monitoring of health claims—and better products. Ernesto Hernandez, PhD, investigates
Food lipids play an important role in nutrition and biological functions as well as in food processing, food quality and the organoleptic and texture properties of food products.1,2 Physiologically, lipids play important roles in most of the biological processes of living organisms, as a source of essential fatty acids, to facilitate absorption of fat-soluble nutrients, and as a source of energy via beta oxidation. Lipid functional foods can be classified into several categories: essential fatty acids (omega-3 and omega-6), fat-soluble vitamins, structured lipids and food/medical supplements.
Once ingested, triglyceride lipids are typically hydrolysed by lipases in the digestive tract into mono-glycerides and free fatty acids and are absorbed in the upper segment of the small intestine. These are then synthesised back into triglycerides in the mucosal epithelial layer and enter the bloodstream as chylomicrons through the lymphatic system. The chylomicrons are metabolised in the liver and incorporated, with cholesterol, into low-density lipoproteins (LDL) and high density lipoproteins (HDL) and then are transported via the bloodstream to the peripheral tissues and organs to perform diverse functions.3
Early studies have shown that diets containing saturated fat increase plasma lipids, and diets rich in polyunsaturated fatty acids (PUFAs) decrease them. However, it is important to differentiate the types of fats—specifically the carbon chain length and number and position of the double bonds in the fatty acid. Also, the ratio of omega-3 and omega-6 PUFAs in the diet plays a major role in the metabolism and physiology of these lipids.4
Saturated fats are a major source of energy, but their intake is monitored and matched to energy expenditure because they tend to increase plasma lipids and cholesterol. Monounsaturated fats have been found to have hyperlipidemic effects and reduce LDL without reducing HDL.5
Nutritional differences in lipid requirements of both infants and adults have led food scientists to modify fats and oils for the production of structured lipids using medium-chain acids and long-chain PUFAs, as well as to develop techniques to concentrate long-chain PUFAs from new and existing sources. Specific targets include improving growth and development of infants, treating disease in adults and preventing disease through the use of omega-3 fatty acids from marine sources.6,7,8,9
Changes in Western eating habits have resulted in an unhealthy imbalance of dietary fatty acids toward an excess of n-6 fatty acids and insufficient levels of n-3 fatty acids. With the exception of stearic acid, excess intake of saturated fats increases LDL levels whilst PUFAs decrease plasma LDL levels—hence the effect of saturated fat intake on coronary disease incidence. Depending on the type, PUFAs play different metabolic and physiological roles (See Figure 2). Conversion of PUFAs into eicosanoids, for example, plays an essential role regarding the onset or control of diseases, such as arthritis and diabetes.
Four main fatty acids can be considered the main precursors of the lipid metabolic pathways in mammals: palmitoleic, oleic, linoleic and linolenic acids. Palmitoleic and palmitic can be synthesised endogenously. However, linoleic and linolenic acids cannot be synthesised and must be obtained from the diet, which is why they are considered essential fatty acids.
Metabolism of omega-6 linoleic acid begins with the catalysis by the enzymes 6-desaturase (acts on carbon 6), 5-desaturase and an elongase to synthesise arachidonic acid, 20:4, n-6 (20 carbon chain length and four double bonds). The desaturation step in the metabolism of alpha-linoleic acid is rate-limiting and the activity rate decreases even more with age. This is the reason for the recommendation that diets be supplemented with oils rich in gamma-linolenic acid.10 Arachidonic acid then becomes part of the synthesis cascade for the formation of eicosanoids with cyclo-oxygenases and lipoxygenases as the catalysts.
The relationship between essential fatty acids and eicosanoids, first reported in the mid-1960s, was described as bioactive compounds derived from arachidonic acid (AA).11 There are two basic types of eicosanoids—prostanoids and leuko-trienes—whose main function is to act as signalling agents in cell-to-cell interactions. Several of these eicosanoids act antagonistically, and an imbalanced production or deficiency can result in the onset of pathological situations such as thrombosis, arthritis inflammation or immune suppression.
For example, the vasoconstrictive effect of the eicosanoid thromboxane has to be balanced by the production of the vasodilator anti-aggregatory prostacyclin.12 Arachidonic acid-derived eicosanoids modulate the production of pro-inflammatory and immunoregulatory cytokines. Overproduction of these cytokines is associated with both septic shock and chronic inflammatory diseases. The n-3 PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are found in fish oils, suppress or modulate the production of arachidonic acid-derived eicosanoids, and EPA is a substrate for the synthesis of an alternative family of eicosanoids.
This illustrates the importance of balancing omega-3 and omega-6 fatty acids because both functional nutrients compete for the same enzymes (desaturases and elongases), but can produce antagonistic types of eicosanoids.
Although the effects of dietary omega-3 and omega-6 are better understood, the effect of different DHA levels on the synthesis of eicosanoids, such as thromboxane (TXA2) and prostacyclin (PGI2) in humans, is still being determined. Some studies suggest the synthesis of TXA2 is more open to diet-induced modulation than the synthesis of PGI2.13
As mentioned earlier, arachidonic acid and EPA are also the precursors of eicosanoids, which influence many cellular processes. When a diet is deficient in linoleic and linolenic acids, palmitoleate and oleate are desaturated and elongated by a desaturase and elingase, respectively, giving rise to eicosatrienoic acids (triene). This lipid is used as a marker for essential fatty acid deficiency. Typical deficiency symptoms include dry skin, reduced growth rate and susceptibility to infection. The recommended intake of linoleic acid is 1 to 2 per cent of the daily calories and linolenic is 0.2 to 0.5 per cent. Their role as precursors for the synthesis of eicosanoids and docosanoids explains many of the multisystemic effects observed when they are administered.
Furthermore, in cases such as preterm births, it has been reported that C-18 omega-3 fatty acids are not sufficiently converted to DHA to allow for biochemical and functional normalcy, thus DHA may be considered a conditionally essential nutrient for normal eye and brain development. Under disease conditions, EPA plays a major role in modifying the balance between omega-6 and omega-3-derived eicosanoids, thus modulating related functions.14
Common vegetable oils, such as non-hydrogenated soybean, cotton and sunflower, are good sources of omega-6 fatty acids (5 to 70 per cent) (See Figure 1). Processing by conventional means doesn't modify their structure significantly. Hydrogenation, on the other hand, will isomerise the polyunsaturated fatty acids from the natural cis configuration to the less nutritionally desired trans structure.
The main sources of omega-3 essential fatty acids are marine oils and oilseed with high content of polyunsaturates such as flax or perilla oils that contain more than 50 per cent alpha-linolenic acid (See Figure 3).
Because these oils are prone to oxidise or isomerise easily, they are processed differently than common vegetable oils. Plant-derived omega-3 oils, such as flax seed, are extracted through pressing processes. Chemical refining is uncommon and processing involves minimal heating. Degumming and refining is conducted at conditions similar to the process used for conventional oils. Deodorising is performed, when necessary, at low temperatures (100š to 150š C) using high-vacuum (10 to 50 mili torrs) and short-residence times (1 to 3 minutes). Deodorising at higher temperatures can induce degradation reaction, such as isomerisation or polymerisation.
The current trend is to market minimally processed oils, particularly if they are plant-derived. However, marine oils, because of their strong odor, require more processing, such as mild chemical refining and molecular distillation.
Vitamin A, found in carotenoids and retinoids, are required for vision and spermatogenesis. Retinol and retinoic acid also play a role in maintaining mucose-secreting cells. Other important functions include modulation of gene expression related to cell differentiation and cell adhesion, which is why vitamin A has been assigned anti-carcinogenic properties.15 Intake requirements for vitamin A are approximately 1.4mg/day and the main sources of this vitamin is dairy foods, meats, fats and oils. Vitamin A is insoluble in water and edible oils are necessary to carry this nutrient through the intestinal mucosa.
Vitamin D regulates calcium and phosphorous metabolism and modulates secretion of polypeptides and hormones. It is also involved in cellular proliferation and differentiation of the immune system. Like vitamin A, it also functions like steroid hormones in gene transcription and expression.16 Milk is the most important dietary source of vitamin D, providing 5 to 10mcg, an adequate daily intake of this nutrient for the general population. However, for the elderly, nutritional supplements that include additional vitamin D and calcium can help prevent osteoporosis and weak bone structure.
Vitamin E primarily controls the peroxidation of PUFAs; it also affects the storage and mobilisation of retinol and complements some of the functions of vitamin A. Vitamin E inactivates free radicals and works in concert with vitamin A to control oxygenases. Vitamin E and tocopherols, in general, minimise peroxidation at a cellular level and thus prevent premature cellular ageing and tissue degenaration.17
The daily recommended intake of vitamin E is 0.4mg/g of linoleic acid. The main source of vitamin E is currently from vegetable oils. The bulk of tocopherols are obtained from deodoriser distillates resulting from vegetable oils processing. There is a relationship between dietary linolenate and vitamin E with prostaglandin biosynthesis.18 Tocopherols and sterols are recovered as by-products from the condensate in the deodorising stage. This distillate typically contains 10 to 30 per cent free fatty acids, 20 to 40 per cent triglyceride material, 10 to 30 per cent tocopherols and 30 to 40 per cent sterols.19,20 The purification steps to obtain tocopherols and sterols fractions includes sequential treatments to remove triglycerides and free fatty acids first, followed by fractionation in a molecular still.
Vitamin K is required for the biological activity of several coagulation factors in the bloodstream in which the clotting factors are produced. Vitamin K may also affect other parameters of bone metabolism, such as calcium hemostasis, prostaglandin E2 and interleukin-6 production. This vitamin is commonly found in green vegetables and its supply doesn't seem to present a problem. Vitamin K is necessary for production of clotting factors II, VII, IX and X in humans. It is also used to prevent osteoporosis. There are two versions of this essential vitamin—vitamin K1 (phylloquinone), primarily found in green leafy vegetables and vitamin K2 (menaquinone), synthesised by certain intestinal bacteria.21
Phytosterols are found in most vegetable oils, usually between 0.1 to 0.5 per cent sterols. Soybean oil, one of the most commonly consumed oils, is reported to contain approximately 0.36 per cent sterols and 0.124 per cent tocopherols.18 Sterols, as well as tocopherols, are usually recovered from deodoriser distillates. This is a by-product from the deodorisation step in vegetable oil processing. The main sterols found in vegetable oils are beta-sitosterol, campesterol and stigmasterol. Phytosterols reportedly interfere with cholesterol absorption and thus prevent the rise in serum cholesterol. Phytosterols also markedly increase the HDL/LDL ratio by upwards of 25 per cent, and also reduce serum cholesterol, possibly by inhibiting the intestinal reabsorption of circulating cholesterol.22
However, phytosterols are not readily metabolised and, in some cases, accumulate in the body. This has led to the development of nutritional supplements called stanols, which are derived from modified sterols. Completely saturated versions of sterols are better metabolised by the body and have been shown to lower cholesterol in clinical trials. The Raisio Group in Finland has developed a margarine called Benecol that has been reported to lower blood cholesterol levels. The compound responsible for this is sitostanol, a 5-a-saturated derivative of sitosterol.23
Phospholipids house synergistic functional and physiological properties that make them attractive candidates for functional foods formulations. They are well known as natural emulsifiers, wetting agents, dispersing agents and liposome formers in foods and pharmaceutical applications. Phospholipids are also being used to enhance the biological activity of other functional lipids, such as CLA.24
The unique emulsifying properties of phosphatides in metabolic systems, such as bile digestive fluids and cell membrane structural and transport systems, make them efficient transport coadjuvants for functional lipids, such as essential fatty acids and fat-soluble vitamins. They ensure miscibility at liquid-liquid and liquid-solid interfaces in many biological pathways.
The main sources of phospholipids are in lecithin from oilseeds, nuts and eggs. The most common types of phospholipids are phosphatidic acid (PA), phosphatidyl choline (PC), phosphatidyl ethanolamine (PE), phosphatidil inositol (PI) and phosphatidyl serine (PS). PS also is the least common, found in only 1 per cent of commercial lecithin from vegetable oils and 3 per cent in commercial lecithin from eggs. PS has been shown to enhance neuronal membrane function and hence cognitive function, especially in the elderly.25 In February 2003, the US Food and Drug Administration authorised two qualified health claims for PS, related to cognitive dysfunction and dementia in the elderly.
Research in the relatively new field of structured lipids (SL) is opening up new avenues of innovation and product development. SL consists of triacylglycerols containing a mixture of short-, medium- and long-chain fatty acids. SL is normally synthesised through lipase-catalysed interesterification reactions.26 The main application of structured lipids (SL) is in the medical field, but applications are being developed in the functional and foods markets. Structured lipids with short- and medium-chain fatty acids are currently used mainly as a source of rapid energy for preterm infants and patients with fat malabsorption-related diseases, as well as for cancer and AIDS patients.
An example of a nutritional product with medical applications is a structured lipid consisting of an interesterified, medium-chain fatty acid, which is absorbed directly into the portal system and provides energy, omega-3 and omega-6 fatty acids that are required to maintain balanced physiological functions.27
An example of a food application of structured lipids is salatrim, which consists of a mixture of long-chain and short-chain fatty acids. Because of the configuration of the fatty acids in the triglyceride and the manner in which lipases metabolise this lipid, it provides 5 calories per gram instead of the 9 calories typical for fats.
Structured lipids are produced by methods that allow the rearrangement and attachment of fatty acids of different chain lengths and other lipids to the glycerol backbone of the triacyglicerol. These methods include interesterification, chemical or enzymatic, genetic engineering, hydrolysis and esterification. The bulk of short- and medium-chain triglycerides used as a quick energy source are obtained from coconut oil and dairy fats through interestrification and fractionation.28
Conjugated linoleic acid (CLA), which is naturally present at low concentrations in some animal fats, has been reported to have bioactive properties. As a result, there is interest in the synthesis and production of CLA as a free fatty acid and in triglyceride form. Recent discoveries—as yet unpublished—have shown that the absorption and utilisation of CLA by the body, as is the case with other fatty acids, is superior if they are esterified to triglycerides such as structured lipids.
CLA has been recently added to the list of nutraceuticals based on a rapidly expanding number of results obtained from many studies in animal systems that show a wide range of biological effects.29 The reported physiological effects of CLA include anti-carcinogenic, anti-atherogenic, reduced fat to lean body mass, improvement of type II diabetes mellitus and immunomodulating properties.30
Natural CLA occurs almost exclusively in fats from animals, mainly ruminants, since CLA is mostly formed during the biohydrogenation of linoleates by rumen bacteria. Researchers at the University of Wisconsin-Madison, by using the lipase from Candida antarctica to directly enrich butteroil with CLA, increased the content of CLA of the triacylglycerides from 0.6 to 15 g/100g fat.31 Enzymatic enrichment of CLA and their incorporation into triacylglycerides has also been described.32 CLA has also been shown to enrich corn oil's lipase content.33 Researchers have recently reported the enzymatic-based preparation of triacylglycerides containing n-3 fatty acids and CLA by acidolysis of fish oil.29
DAG oils contain two fatty acids on the carbons 1 and 3 of the glycerol fat molecule instead of three normally found in conventional oils. They are produced commercially by interesterification. Diacylglycerols have been shown to have different metabolic effects compared to conventional edible oils. It has been shown that 1,3-diacylglycerols are metabolised preferentially as energy rather than being stored as fat. Published studies have shown that regular consumption of diacylglycerol oil as part of a sensible diet can help individuals manage their body weight and body fat.34,35 Also, 1,3-diacylglycerol has been shown to reduce circulating postmeal triglycerides in the bloodstream. Examples of food products where DAG oils are used are mayonnaise and baked products.36
The application of these designer fats in the food industry is new territory. Consequently, for each newly developed type of structured lipids, it is necessary to build a working knowledge of which ratios of fatty acids, and in what specific positions of fatty acids on the triacylglyceride molecule, will yield the fat that best meets the target objectives.
Although healthful fats have been recognised for a century, the physiological effect of functional lipids in general is only recently being better understood. For the first time, government health institutions are recommending adequate intakes and ratios of specific essential fatty acids. However, as we increase our knowledge of lipid biological pathways and discover new lipid nutraceuticals, we need to educate the general public on the uses of these new products. The consumption of functional lipids along with other nutraceuticals will continue to increase as the population becomes older. Therefore, the choice of a diet has become not just a means of weight control, but metabolism control and disease prevention. Functional lipids will play a key role.
Ernesto Hernandez, PhD, is associate research engineer and head of the Food Protein R&D Center, Texas A&M University. firstname.lastname@example.org
1. Dupont J, et al. Fatty acid-related functions. Am J Clin Nutr 1996;63(6):991S-3S.
2. Kinsella JE. Food lipids and fatty acids: importance in food quality, nutrition and health. Food Technol 1988;42 (10):124-42.
3. Mead JF. Lipids: chemistry, biochemistry and nutrition. New York: Plenum Press, 1986.
4. Holman RT. The slow discovery of the importance of omega-3 essential fatty acids in human health. J Nutr 1998;128(2S):427S-33S.
5. Grundy SM. Cholesterol and coronary artery disease. JAMA 1986;256:2849-58.
6. Uauy DR, Valenzuela A. Marine oils as a source of omega-3 fatty acids in the diet: How to optimize the health benefits. Prog Food Nutr Sci 1992;16(3):199-243.
7. Karlsson J, et al. Plasma omega-3 fatty acids before and after nutritional therapy. J Nutr Environ Med 1998;8(1):25-34.
8. Mamalakis G, et al. Anxiety and adipose essential fatty acid precursors for prostaglandin E1 and E2. J Am Coll Nutr 1998;17(3):239-43.
9. Simopoulos AP. Essential fatty acids in health and chronic disease. Food Rev Int Marcel Dekker Inc 1997;13(4):623-31.
10. Carter JP. Gamma linolenic acid as a nutrient. Food Tech 1988;42(6):72.
11. Van Dorp DA, et al. The biosythesis of prostaglandins. Biochim Biophys Acta 1964;90:204.
12. Faggiotto A. Cellular dynamics in atherosclerosis. In, "Health Effects of Polyunsaturated Fatty Acids in Seafoods," Simopoulous A, Kifer R, and Martin RE. p 87. Academic Press, Orlando FL. 1986.
13. Ferretti A, et al. Dietary docosahexaenoic acid reduces the thromboxane-prostacyclin synthetic ratio in humans. J Nutr Biochem 1998;9(2):88-92.
14. Sardesai VM. Nutritional role of polyunsaturated fatty acids. J Nutr Biochem 1992;3(4):154-66.
15. Olson JA. 1987. Recommended dietary intakes (RDI) of vitamin A in humans. Am J Clin Nutr 1987 Apr;45(4):56.
16. De Luca H. Vitamin D metabolism. In "Modern nutrition in health and disease" (Young V, Shils M, Eds) Lea and Fabiger Press, Philadelphia, PA. 1988.
17. Farrell PM. Vitamin E. In "Modern nutrition in health and disease" (Young, V. Shils, M. Eds.) Lea and Fabiger Press, Philadelphia, PA. 1988.
18. Dupont J. Essential fatty acids and prostaglandins. Prev Med 1987;16(4):485-92.
19. Hoffman RL, et al. J Am Chem Soc 1964;41:116.
20. Marks CT. Tocopherols in deodorizer distillate. J Am Oil Chem Soc 1988;65:881-2.
21. Conly JM. The production of menaquinones (vitamin K2) by intestinal bacteria and their role in maintaining coagulation homeostasis. Prog Food Nutr Sci 1992;16(4):307-43.
22. Pellerier X, et al. A diet moderately enriched in phytosterols lowers plasma cholesterol concentrations in normocholesterolemic humans. Ann Nutr Metab 1995;39:291-5.
23. Reese KM. Benecol. Chem Engineer News 1996;74(Aug):68.
24. Hossen M, Hernandez E. Enzyme catalyzed synthesis of structures phospholipid with CLA: potential therapeutic agent. Am Oil Chem Soc Ann Meetings Abstr 2003. p.34.
25. Crook TH, et al. Effects of phosphatidylserine in age-associated memory impairment. Neurology 1991 May;41(5):644-9.
26. Willis WM, et al. Lipid modification strategies in the production of nutritionally functional fats and oils. Crit Rev Food Sci Nutr 1998;38(8):639-74.
27. Fitch-Haumann B. Structured lipids allow fat tailoring. INFORM 1997;8(10):1004-11.
28. Merolli A. Medium-chain lipids: new sources, uses. INFORM 1997;8(6):597-603.
29. Garcia HS, et al. Synthesis of glycerides containing n-3 fatty acids and conjugated linolenic acid by solvent-free acidolysis of fish oil. Biotechnol Bioeng 2000;70:587-91.
30. Gnadig S, et al. Conjugated linoleic acid (CLA): physiological effects and production. J Lipid Sci Tech 2001;103:56-61.
31. Garcia HS, et al. Enrichment of butteroil with conjugated linoleic acid via enzymatic interestrification (acidolysis) reactions. Biotechnol Lett 1998;20:393-5.
32. McNeill GP, et al. Enzymatic enrichment of conjugated linoleic acid isomers and incorporation into triglycerides. J Am Oil Chem Soc 1999;76:443-50.
33. Martinez CE, et al. Lipase-catalized interesterification (acidolysis) of corn oil and conjugated linoleic acid in organic solvents. Food Biotechnol 2000;13:183-93.
34. Maki, et al. Consumption of diacylglycerol oil as part of a reduced-energy diet enhances loss of body weight and fat in comparison with consumption of a triacylglycerol control oil. Am J Clin Nutr 2002;76:1230-6.
35. Nagao, et al., Dietary diacylglycerol suppresses accumulation of body fat compared to triacylglycerol in men in a double-blind controlled trial. J Nutr 2000;130:792-7.
36. Sikorski, et al. Applications of diacylglycerols oils in foods. Am Oil Chem Soc Annual Meetings Abstracts 2003:42.