Fats are hydrophobic hydrocarbon molecules consisting of fatty acids and glycerol. Glycerol has three carbons, each of which is attached to a hydroxyl group. Most fats are formed through replacement of the hydrogen of each hydroxyl group by a fatty acid. As three chains of fatty acids can be attached to each glycerol molecule, the resulting molecule is called a triglyceride.
Medium chain triglycerides (MCTs) are composed of fatty acids that contain between 6 and 12 carbon atoms compared to the 14 or more carbon atoms in long chain triglycerides (LCTs).
Fats can be further characterised by the number of double bonds in the fatty acid chain. Monounsaturated fatty acids (MUFAs) have one double bond in the chain, whereas polyunsaturated fatty acids (PUFAs) have more. Unsaturated fats are named according to the position of the double bonds: counting from the non-glycerol end of the fatty acid, the first double bond encountered in an omega-3 (ω-3) fatty acid is at the third carbon.
Eicosanoids are signalling molecules made by oxygenation of twenty-carbon fatty acids.1
Some fatty acids that are released in the process of digestion are called essential because they cannot be synthesised in the body from simpler constituents: alpha-linolenic acid (an ω-3 fatty acid) and linoleic acid (an ω-6 fatty acid). Other lipids needed by the body can be synthesised from these and other fats. Fats and other lipids are broken down in the body by enzymes called lipases produced in the pancreas.
Fats provide energy for the body, and can be stored as adipose tissue when consumed in excess of immediate needs. Each gram of fat releases about 9 food calories (37 kJ = 8.8 kCal). Fats are broken down to release glycerol and fatty acids, and glycerol can be converted to glucose by the liver and so become a source of energy.
Vitamins A, D, E, and K are fat-soluble, meaning they can only be digested, absorbed, and transported in conjunction with fats. Lipids are a key component of cell membranes, where they modulate membrane fluidity which affects membrane-bound receptors and enzymes.2 They are involved in precursor synthesis, provide the building blocks for synthesis of cholesterol and fat-soluble vitamins, and regulate, blood pressure, blood clotting, inflammation and the corresponding immune response.
There is an inverse, dose-dependent relationship between the intake of linoleic acid (LA) and blood low-density lipoprotein (LDL) cholesterol concentrations, and a direct relationship with high-density lipoprotein (HDL) concentrations.3 As LDL levels increase, so does CVD risk.4 HDL cholesterol is inversely associated with the risk of developing CVD, as it directly protects against the development of atherosclerosis.4
LA lowers fasting blood triacylglycerol concentrations compared to carbohydrates.3 There is also evidence that replacement of saturated fatty acids by ω-6 PUFAs (without changing total fat intake) decreases the number of cardiovascular events in the population.3
Eicosanoids exert complex control over many bodily systems, mainly in inflammation, immunity, and as messengers in the central nervous system. The networks of control that depend upon eicosanoids are among the most complex in the human body. There are three main subgroups of eicosanoid:
- Cytokines: signalling molecules used extensively in cellular communication
- Prostaglandins: a group of lipid compounds derived enzymatically from fatty acids.
- Leukotrienes: naturally produced eicosanoid lipid mediators, partly responsible for the effects of the inflammatory response.
In general, ω-6 fatty acids are pro-inflammatory and ω-3 fatty acids are anti-inflammatory.5 The common ω-3 and ω-6 fatty acids are shown in Figure 1. (Figure 6.2.2. from Peptamen Family Fact Book)
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Increased levels of ω-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA, both found in cold-water fish):
- dynamically displace ω-6 fatty acids from the cell membranes of immune cells, reducing systemic inflammation through the production of biologically less active prostaglandins and leukotrienes.6
- downregulate expression of nuclear factor-kappa B, intracellular adhesion molecule 1, and E-selectin, decreasing neutrophil attachment and trans-epithelial migration to modulate systemic and local inflammation.6
- help stabilise the myocardium and lower the incidence of cardiac arrhythmias, decrease incidence of ARDS, and reduce likelihood of sepsis.6-8
Figure 2 (Figure 6.2.3 from Peptamen Family Fact Book) shows the main pathway for the production of pro-inflammatory compounds from ω-6 fatty acids and anti-inflammatory compounds from ω-3 fatty acids.
Dietary fat is primarily consumed as triacylglycerol, while other forms include cholesterol and free fatty acids.
Recommendations for total fat intake in adults are set by the Daily Recommended Intakes. Fat should provide between 20 and 35% of calories for men and women aged over 30 years.9
The FAO/WHO 2008 recommend a total PUFA consumption of between 6 and 11% total energy (E), as the risk of lipid peroxidation may increase above this level. The lower level is intended to decrease LDL and total cholesterol, increase HDL and decrease the risk of CHD events. They recommend that saturated fatty acids (SFA) in the diet should be replaced by PUFAs (ω-6 and ω-3).10
There should be a minimum intake of 2.5%E linoleic acid and 0.5%E α-linolenic acid to prevent deficiencies of essential fatty acids.10
Studies have not separated EPA and DHA intakes, so there is no specific recommendation for the single oils. The recommended intake for EPA+DHA is defined either as the amount of fish that should be consumed or the absolute quantities of EPA+DHA, typically between 250 and 600 mg/day.
The ratio of ω-6 : ω-3 fatty acids can affect the patient response to disease by favouring either the inflammatory or anti-inflammatory pathway of eicosanoid production.
Role of fats in illness
Fats are hydrophobic and are therefore emulsified by bile salts and phospholipids as a first stage in digestion. Pancreatic lipase works at the surface of the emulsified droplets to break them into monoglycerides and fatty acids which are then transported to the surface of the enterocyte. Once inside, the components are re-synthesised into chylomicrons before entering lymphatic capillaries and eventually the bloodstream. MCTs are absorbed in the duodenum faster than LCTs, being taken directly into the portal system and transported to the liver without the need for bile salts, and are readily hydrolysed by pancreatic lipase.11,12
Figure 3. (Figure 3 from Isosource Family Regulatory Dossier).
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MCTs are not stored as adipose tissue, but are rapidly metabolised to ketone bodies, providing a readily available non-carbohydrate energy source. MCTs are thus a good energy source for patients with fat malabsorption.13
During times of malnutrition, stress or if the GI tract is compromised, LCT malabsorption is very common. Fat malabsorption is characterised by bulky, frothy, voluminous, loose stool, but can be improved by providing formulas rich in MCT oil to minimise risk of fat malabsorption.
Stress related to acute diseases and drugs may decrease GI motility and gastric emptying, increasing the risk of reflux and lung aspiration. MCTs are well tolerated, as they are emptied from the stomach faster than LCT.14 It has been shown that the absorption of unsaturated fatty acids is inversely proportional to their chain length.15
As MCTs are easily absorbed and hydrolysed they are suitable for malnourished patients with reduced lipase activity and bile production.16,17 MCTs also provide more readily available energy than LCTs. Enteral formulas containing 25 to 50% MCT are commonly used in patients requiring intensive clinical nutrition.18 This ensures a supply of essential fatty acids from the LCT and better digestion, absorption and metabolism due to the MCT.18-20
Fish oil is used to help control inflammation associated with critical and chronic illness.21 Typically, fish oil triglycerides contain one highly unsaturated fatty acid and two saturated fatty acids. The triglyceride is broken down to two free fatty acids and a monoglyceride for absorption from the GI tract. The fatty acids and monoglyceride are reassembled and transported in the body for use as ingredients for cell components, active molecules, or storage in adipose tissue as an energy reserve.22
In the critical care setting, it is important to modulate the inflammatory response to avoid excessive inflammation. The typical western diet has a ω-6 : ω-3 fatty acid ratio of > 15:123 which is pro-inflammatory. There is no broad consensus on the optimal ω-6 : ω-3 ratio other than that a relatively low ratio is beneficial for the critically ill patient.
Supplementation of feeds
MCTs are an energy dense, well absorbed nutrient used to provide energy to patients suffering from impaired absorption of LCTs. MCTs are not considered to be essential nutrients, but are added to EN products to aid digestion,16 absorption in the upper portion of the small intestine.17 They are well tolerated when used in formulas that are designed to be readily absorbed,13 and do not require pancreatic lipase or bile for digestion and absorption.13 Typical levels range up to 70% of the lipid calories.
Some enteral formulas contain MUFAs and PUFAs for glycaemic benefit. For example, a recent study showed that Type II diabetes patients who received 12 weeks of a high MUFA formula (32% of energy) achieved better glycaemic control compared to patients who received a standard tube feed formula.24
Canola oil is another source of fat that can be added to enteral formulas. Canola oil is characterised by a low level of saturated fat (7%), substantial amounts of MUFAs and PUFAs, including 61% oleic acid, 21% linoleic acid and 11% ALA.25 A recent review found it to be beneficial in suppressing triglyceride and LDL-C levels26, enhancing fatty acid oxidation27, and exerting anti-thrombotic and anti-oxidative effects.28
Historically, MCTs have been used in nutrition therapy for cases of disturbed digestion, absorption, or transport of dietary fat.19
In contrast, LCT digestion, absorption, and transport are more complex processes requiring chylomicron formation and secretion into the lymphatic system.
- Gonzalez-Periz AC. Resolution of adipose tissue inflammation. Scientific World J 2010;10:832-56.
- Das UN. Essential fatty acids - a review. Curr Pharm Biotechnol 2006;7:467-82.
- EFSA. Panel on Dietetic Products, Nutrition and Allergies. Scientific Opinion on Dietary Reference Values for fats, including saturated fatty acids, polyunsaturated fatty acids, monounsaturated fatty acids, trans fatty acids, and cholesterol. EFSA Journal 2010;8:1461.
- Expert Panel on Detection and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-97.
- Wall R, Ross RP, et al. Fatty acids from fish: the anti-inflammatory potential of long-chain omega-3 fatty acids. Nutr Rev 2010;68:280-9.
- McClave SA, Taylor BE. Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (ASPEN). JPEN 2016;40:159-211.
- Singer P, Theilla M, et al. Benefit of an enteral diet enriched with eicosapentaenoic acid and gamma-linolenic acid in ventilated patients with acute lung injury. Crit Care Med 2006;34:1033-8.
- Pontes-Arruda A, Aragao AM. Effects of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in mechanically ventilated patients with severe sepsis and septic shock. Crit Care Med 2006;34:2325-33.
- DRI. Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids. Food and Nutrition Board, Institute of Medicine, National Academy of Science 2005.
- FAO/WHO. From the Joint FAO/WHO Expert Consultation on Fats and Fatty Acids in Human Nutrition, November 10-14. WHO HQ, Geneva 2008.
- Gottschlich MM. Selection of optimal lipid sources in enteral and parenteral nutrition. Nutr Clin Pract 1992;7:152-65.
- Mahan LK. Krause’s Food Nutrition & Diet Therapy. 9th edition. 9th edition ed. Philadelphia: W B Saunders; 1996.
- Salomon S, Jung J, Voss T, Suguitan A, Rowe W, Madsen D. An elemental diet containing medium-chain triglycerides and enzymatically hydrolyzed protein can improve gastrointestinal tolerance in people infected with HIV. J Am Diet Assoc 1998;98:460-2.
- Bach AC, Ingenbleek Y, et al. The usefulness of dietary medium-chain triglycerides in body weight control: fact or fancy? J Lipid Res 1996;37:708-26.
- Spencer S, McKenna S. Two different low birth weight formulae compared. Early Hum Devel 1992;30:21-31.
- Metges C, Wolfram G. Medium-and long chain triglycerides labeled with 13C:a comparison of oxidation after oral or parenteral administration in humans. J Nutr 1991;121:31-6.
- Hopman W, Jansen J, Rosenbusch G, Lamers C. Effect of equimolar amounts of long-chain triglycerides and medium-chain triglycerides on plasma cholecystokinin and gallbladder contraction. Am J Clin Nutr 1984;39:356-9.
- Simopoulos AP. Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr 2002;21:495-505.
- Bach AC, Babayan VK. Medium-chain triglycerides: an update. Am J Clin Nutr 1982;36:950-62.
- Blackburn GL. Nutrition and inflammatory events: highly unsaturated fatty acids (omega-3 vs omega-6) in surgical injury. Proc Soc Exp Biol Med 1992;200:183-8.
- Calder PC. Omega-3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology? Br J Clin Pharmacol 2013;75:645-62.
- Caspary WF. Physiology and pathophysiology of intestinal absorption. Am J Clin Nutr 1992;55:S299-308.
- Simopoulos AP. Importance of the ratio of omega-6/omega-3 essential fatty acids: evolutionary aspects. World Rev Nutr Diet 2003;92:1-22.
- Pohl M, Mayr P, Mertl-Roetzer M, et al. Glycemic control in type II diabetic tube-fed patients with a new enteral formula low in carbohydrates and high in monounsaturated fatty acids: a randomised controlled trial. Eur J Clin Nutr 2005;59:1221-32.
- Lin L, Allemekinders H, Dansby A, et al. Evidence of health benefits of canola oil. Nutr Rev 2013;71:370-85.
- Lichtenstein A, Ausman L, Carrasco W, et al. Effects of canola, corn and olive oils on fasting and postprandial plasma lipoproteins in humans as part of a national cholesterol education program step 2 diet. Aterioscler Thromb 1993;13:1533-42.
- Corboy J. Fatty acid composition and the oxidation of low-density lipoproteins. Biochem Med Metab Biol 1993;49:25-35.
- Sodergren E, Gustafsson B, Basu S. A diet containing rapeseed oil-based fat does not increase lipid peroxidation in humans when compared to a diet rich in saturated fatty acids. Eur J Clin Nutr 2001;55:922-31.