Parrillo Performance
800-344-3404

The components of energy expenditure are illustrated in figure 1. Metabolic rate is affected by many parameters such as eating (caloric consumption as well as dietary com-position), activity (dependent on type, intensity, and duration of activity), lean body mass, age, sex, hor-mones, and drugs .Since all of the energy expended by the body is ultimately converted to heat (except when work is performed outside the body), metabolic rate can be determined by the amount of heat energy liberated by the body (Guyton, 1976). A calorimeter can be used to directly measure the heat given off by the body. However, since greater than 95% of the energy lib-erated by the body is derived from the reaction of foods with oxygen, the metabolic rate can also be calculated from the rate of oxygen consumption (Guyton, 1976). In many studies metabolic rate, or energy expenditure, is expressed in terms of oxygen consumption.Thermic Effect of Feeding Medium Chain TriglyceridesAfter consuming a meal the food is digested, released into the bloodstream, and transported to all the cells of the body. There, it reacts with oxygen to produce en-ergy. Some of the energy is captured in ATP, the energy source used directly by cellular machinery performing work.

Calories consumed in excess of energy require-ments will be stored as body weight. About 55% of the energy contained in food is liberated as heat during the process of ATP formation (Guyton, 1976). This release of heat energy from the oxidation of foods rep-resents an increase in metabolic rate and is accompanied by increased oxygen consumption .Feeding different dietary items while maintaining caloric intake affects oxygen consumption (Baba, Bracco, and Hashim, 1982). That different foods, normalized for energy content, increase the metabolic rate to different extents probably reflects the tendency of a particular food to be burned for energy versus being stored as body weight, as well as its extent of digestion and absorption. That protein increases the metabolic rate more than carbohydrate and conventional fat sug-gests that certain amino acids may directly stimulate thermogenesis (Guyton, 1976). The increase in energy expenditure caused by feeding is known as diet-induced thermogenesis or the thermic effect of feeding (Van Zant, 1992). MCTs cause profound postprandial thermogen-esis because they are very caloric dense and are absorbed and metabolized very rapidly.

The rapid oxidation of MCFAs in the liver causes an increase in postprandial oxygen consumption, i.e. metabolic rate. The increase in metabolic rate resulting from MCT ingestion has been measured in humans as well as in rats, using LCTs as con-trols (Seaton et al, 1986; Hill et al, 1989; Baba, Bracco, and Hashim, 1982). The data seem straight forward, well controlled, and statistically significant. Baba, Bracco, and Hashim (1982) observed that rats overfed MCT gained significantly less fat than rats fed an isocaloric diet containing LCT as the fat source. This was attributed to higher resting oxygen consumption (metabolic rate) in the MCT group. The authors ex-plained this by pointing out that while conventional fats are transported as chylomicrons and are largely stored as body fat, MCTs are transported directly to the liver where they are oxidized extensively to produce energy. The rapid oxidation of MCTs results in increased oxygen consumption, increased heat generation, and increased metabolic rate. In 1986 Seaton and colleagues demonstrated in humans that a meal containing MCTs increased oxygen consump-tion 12% above basal levels for 6 hours following the meal, while the LCT-containing meal increased oxygen consumption by only 4%. This indicates that MCTs are burned faster than conventional fats and increase the metabolic rate more. The increase in energy expenditure accounted for 13% of the energy contained in the MCT meal and 4% of the energy contained in the LCT meal. Hill and coworkers (1989) also compared the thermo-genic effect of medium chain triglycerides with that of long chain triglycerides.

Ten male volunteers were hospitalized and fed diets containing 30% of calories from either MCT or LCT. Metabolic rate was measured before, during, and after the experiment. Each subject was studied for one week on each diet in a double-blind crossover design. The thermic effect of food (TEF) is defined as the difference between metabolic rate during a six hour period after eating and the resting metabolic rate. That is, it is a measure of the increase in metabolic rate caused by eating the test meal. On day one of the experiment, the TEF of the meal containing MCT ac-counted for 8% of the ingested energy, while the TEF of the LCT meal accounted for 5.5% of the ingested energy. On day six of the experiment, the TEF of the MCT meal had increased to 12% of ingested energy, and the TEF of the LCT meal was 6.6% of ingested energy (figure 2). This means that the MCT-enhancement of the metabolic rate increased during the course of the experiment as the subjects became acclimated to the MCTs. On the last day of the trial the subjects were fed a liquid diet by continuous tube feeding.

During this experiment it was found that the TEF of the MCT meal increased to 15.7% of ingested energy, and the TEF of the LCT meal was 7.3% of ingested energy. So the increase in metabolic rate was even greater when MCT was administered continually .Mechanisms of ThermogenesisThe chemical mechanism underlying this thermogenic effect is unknown at present, but several suggestions have been advanced. Hill and coworkers (1989 and 1990) demon-strated that MCT overfeeding results in in-creased hepatic de novo fatty acid synthesis in man. This process is energetically costly and could account for the lesser efficiency of storage of MCT-derived energy. The observed increase in thermogenesis agrees well with the energy cost associated with de novo lipogenesis (Hill et al, 1990). This observation was corroborated by Crozier (1988) working with isolated rat hepatocytes.Alternatively, if electron transport is uncoupled from oxidative phosphorylation the energy spent to es-tablish an electrochemical potential gradient across the mitochondrial membrane is dissipated as heat instead of being conserved as ATP (Baba, Bracco, and Hashim, 1987).

For example, in brown adipose tissue a pathway exists allowing proton leakage across the mitochondrial membrane (Nicholls, 1979).Another means of dissipating energy as heat, believed to occur in liver mitochondria, is redox cycling involv-ing the glycerophosphate and malate shuttles (Berry et al, 1985; Crozier et al, 1987). In the glycerophosphate shuttle, energy is spent to pump reducing equivalents outside the mitochondria to drive the reduction of di-hydroxyacetone phosphate to glycerol-3-phosphate in the cytoplasm. The glycerol-3-phosphate then diffuses into the mitochondria and is oxidized to reform dihy-droxyacetone phosphate, which then diffuses out of the mitochondria to complete the cycle . The net result is the shuttle of glycerol-3-phosphate and dihydroxyacetone phosphate across the mitochondrial membrane (Berry et al, 1985; Crozier et al, 1987; Zubay, 1983, p. 401). Free energy is consumed to drive the cycle, but since no net work is performed the energy ultimately appears as heat (Berry et al, 1985).

The malate/aspartate shuttle is analogous .  Finally, increased activity of Na-K ATPase has also been suggested as a thermogenic mechanism for wasting en-ergy as heat (Levin and Sullivan, 1985). It is estimated that 10-40% of the total energy expended by the cell is used to maintain the concentration gradient of sodium and potassium ions across the cell membrane (Vander, Sherman, and Luciano, 1980). Since these ions also can cross the membrane by passive diffusion, an increase in the activity of the enzyme could be a mechanism for spending ATP.In all of the models - de novo fatty acid synthesis, proton leakage, redox cycling (or other futile cycles), and Na-K ATPase - the MCFAs are rapidly oxidized (explaining increased oxygen consumption), energy is consumed (explaining the low efficiency of storage of MCT-derived energy) and heat is produced as a by-prod-uct (explaining the thermogenic effect). Considerable evidence exists to support the involvement of de novo fatty acid synthesis as a mechanism for MCT-induced thermogenesis (Hill et al, 1989; Hill et al, 1990; Crozier, 1988) but other mechanisms may be involved as well. The reader is referred to Levin and Sullivan (1985) and Van Zant (1992) for reviews on thermogenesis and en-ergy balance.

References

1. Baba, Bracco, and Hashim, Enhanced thermogen-esis and diminished deposition of fat in response to over-feeding with diet containing medium chain triglyceride. Am. J. Clin. Nutr. 35: 678-682 (1982).

2. Baba, Bracco, and Hashim, Role of brown adipose tissue in thermogenesis induced by overfeeding a diet containing medium chain triglyceride . Lipids 22: 442-444 (1987).

3. Berry, Clark, Grivell, and Wallace, The contribu-tion of hepatic metabolism to diet-induced thermogenesis . Metab. 34: 141-147 (1985).

4. Crozier, Medium chain triglyceride feeding over the long term: the metabolic fate of C-14 octanoate and C-14 oleate in isolated rat hepatocytes. J. Nutr. 118: 297-304 (1988).

5. Crozier, Bois-Joyeux, Chanez, Girard, and Peret, Metabolic effects induced by long-term feeding of medium chain triglycerides in the rat. Metabolism 36: 807-814 (1987).

6. Guyton, Textbook of Medical Physiology. Pub-lished by W.B. Saunders, chapter 71 (1976).

7. Hill, Peters, Yang, Sharp, Kaler, Abumrad, and Greene, Thermogenesis in humans during overfeeding with medium chain triglycerides. Metabolism 38: 641-648 (1989).

8. Hill, Peters, Swift, Yang, Sharp, Abumrad, and Greene, Changes in blood lipids during six days of over- feeding with medium or long chain tri-glycerides. J. Lipid Res. 31: 407-416 (1990).

9. Levin and Sullivan, Regulation of thermogenesis in obesity. In: Novel Approaches and Drugs for Obesity, eds. Sullivan and Garattini, John Libbey and Co. Ltd. (1985).

10. Nicholls, Brown adipose tissue mitochondria. Bio-chim. Biophys. Acta 549: 1-29 (1979).

11. Seaton, Welle, Warenko, and Campbell, Thermic effect of medium chain and long chain triglycerides in man. Am. J. Clin. Nutr. 44: 630-634 (1986).

12. Vander, Sherman, and Luciano, Human Physiology - The Mechanisms of Body Function, p. 236. Published by McGraw-Hill Book Company, 1980 .

Parrillo Performance
800-344-3404

The reaction between hydrogen and oxygen to make water is extremely exergonic (this is the reaction that turned the Hindenburg into a fireball). This reaction releases energy because hydrogen and oxygen are more stable (i.e., have less energy) when they are joined together as water than when they exist separately. Most of the energy derived from the aero-bic metabolism of foods is from this reaction. Fats provide twice the caloric density of carbohydrates - 9 calories per gram for fat as compared to 4 calories per gram for carbohydrate. The reason fat contains more energy than carbohydrate is that in fat the carbon is in a more reduced form (Zubay, 1983, p. 482) - more hydrogen is packed in per carbon atom. In aerobic metabolism the carbon and hydrogen in foods react with oxygen to produce CO2 and H2O. This reaction releases energy because carbon diox-ide and water molecules contain less energy than the original food molecules and oxygen.

The same reac-tion occurs when a piece of food burns in the camp fire. In that situation the energy released by the reac-tion is simply liberated as heat to the surroundings. In the body the reaction is broken down into many small steps and the energy which is released is captured in a molecule called adenosine triphosphate, or ATP. About 67% of the energy obtained in glucose (the body’s chief fuel molecule) is captured by ATP and the rest is liberated as heat (Zubay, 1983, p. 395). This is a very impressive efficiency level compared to other machines. ATP is the immediate source of energy used to fuel nearly all cellular processes, including muscular contraction. The role of ATP is not to store energy (that is the role of body fat and glycogen) but rather to transfer energy from a food molecule to some other cellular molecule which is going to perform work (Vander, Sherman, Luciano, 1980, p. 80). Ener-gy is the ability to do work. Potential energy is energy which is stored and has the potential to perform work if it is released. The energy contained in a chemi-cal bond is a form of potential energy. The potential energy contained in the chemical bonds of food mol-ecules is released during oxidation, and this energy is transferred via ATP to other molecules which perform cellular work - everything from muscular contraction to protein synthesis .

Conceptually, it is convenient to break up this process into four stages, although in fact these stages are inti-mately linked in the cell. The first stage of carbohy-drate metabolism is glycolysis and the first stage of fat metabolism is beta-oxidation. The following stages of energy production are common to both fats and carbo-hydrates, and are the Krebs cycle, electron transport, and oxidative phosphorylation. The Krebs CycleThe central energy producing pathway in the body is the Krebs cycle (figure 1), named for the German chemist Hans Krebs. Krebs originally postulated this process, also known as the TCA cycle, in 1937 and was later awarded the Nobel Prize in 1953 for this work. Energy substrates derived from carbohydrates or fatty acids enter the Krebs cycle as the intermedi-ate acetyl-CoA. The ultimate end of the process is to convert the chemical energy contained in foods into ATP.

Adenosine triphosphate is an unstable molecule containing a high energy phosphate bond. When ATP is split, the energy contained in this phosphate bond is released and is available to perform work inside the cell. ATP is the immediate source of energy for nearly all cellular processes, and thus has earned its reputa-tion as “the energy currency of the cell.”Carbohydrates are initially metabolized via an anaerobic process known as glycolysis. Glu-cose enters the glycolytic pathway and is con-verted into two molecules of pyruvate, generat-ing a net yield of two ATP molecules. Under anaerobic conditions, as may be temporarily experienced in muscular tissue during weight training, pyruvate is reduced to lactate, or lactic acid, which causes a burning sensation in the muscle. Glycolysis is a relatively inefficient process, yielding only two ATPs per glucose molecule. The two lactate molecules account for roughly 93% of the energy present in the original glucose molecule, so only about 7% of the energy embodied in glucose is made avail-able for use. Of this, about 50% is captured in ATP (Zubay, 1983, p. 305).

In the presence of oxygen a different metabolic fate is available to pyruvate. Instead of being converted into lactate, pyruvate is decarboxylated to generate acetyl-CoA. Acetyl-CoA is also produced by beta-oxidation of fatty acids, as discussed Tech-nical Report #2.The basic point of the Krebs cycle is to provide the chemical means of completely oxidizing the carbon of glucose or fatty acids to CO2 and the hydrogen to H2O. This allows much more of the energy contained in the food molecule to be extracted and used by the cell, as compared to anaerobic metabolism. In each turn of the Krebs cycle two carbons enter as acetate and two carbons exit as CO2. The cycle involves eight intermediates, each of which is converted into the next by an enzyme specific for that step (figure 1). These reactions are localized in the mitochondria, the site of aerobic energy production within the cell. The first stage of carbohydrate metabolism, glycolysis, occurs in the cytoplasm and does not require oxygen.

The end-product of glycolysis, pyruvate, enters the mitochondria to be further metabolized. In the mi-tochondria pyruvate is converted into acetyl-CoA by pyruvate dehydrogenase. Fats are oxidized to produce acetyl-CoA within the mitochondria. Long chain fatty acids must be ferried across the mitochondrial mem-brane by the carnitine shuttle, while medium chain fatty acids can transverse the membrane by passive diffusion.Acetyl-CoA donates the two-carbon compound acetate to a four-carbon acceptor oxaloacetate thereby gener-ating citrate, a six-carbon compound. During one turn of the cycle two molecules of carbon dioxide are liber-ated, ultimately regenerating oxaloacetate. The Krebs cycle intermediates are not consumed in the cycle and there is no net loss of carbon in the process, ignoring any side reactions which may occur. The cycle can thus be viewed as catalytic, since a relatively small amount of oxaloacetate can be used to metabolize an arbitrary amount of acetyl-CoA.

The activity of this pathway is controlled by the levels of its substrates and products, so that its level of energy production matches the energy needs of the cell. As the concentration of substrates increases, or the concentration of end products decreases, the activ-ity of the cycle increases. The most sensitive factors which directly regulate the cycle’s activity are the NAD/NADH ratio and the ATP/ADP ratio. The activ-ity of the first step in the pathway is also sensitive to the concentration of oxaloacetate.Under normal conditions the concentration of interme-diates such as oxaloacetate is not limiting. Medium chain triglycerides enter mitochondria independent of the carnitine shuttle, and thus bypass an important regulatory step in fatty acid oxidation (refer to Techni-cal Report #2). Medium chain triglycerides are oxi-dized so rapidly that the acetyl-CoA which is produced can overwhelm the amount of oxaloacetate available to accept it (Bach and Babayan, 1982). Some portion of the acetyl-CoA is then diverted to another metabolic fate - ketogenesis. In ketogenesis two molecules of acetyl-CoA combine to form ketone bodies, primar-ily acetoacetic acid and beta-hydroxybutarate (refer to Technical Report #2). This process is diminished if oxaloacetate precursors, such as aspartate and pyru-vate, are co-administered with the MCTs (Bach and Babayan, 1982; Crozier, 1988).

This suggests that the ketogenic properties of MCTs are due, in fact, to their ability to overwhelm the capacity of the Krebs cycle at the level of oxaloacetate.Only one ATP molecule is produced directly by each turn of the Krebs cycle. This is referred to as “sub-strate level phosphorylation” since the generation of ATP is directly coupled to a specific chemical reaction. In other words, ADP participates as a substrate in the reaction. Most of the energy derived from aerobic metabolism comes from subsequent oxidation of the NADH and FADH2 produced by the cycle. This is referred to as “oxidative phosphorylation” since here ATP synthesis is coupled to the oxidation of NADH and FADH2. Aerobic metabolism can the be thought of as having two phases: the oxidative phase in which electrons (in the form of hydrogen atoms) are removed from organic substrates and transferred to coenzyme carriers (FAD and NAD), followed by the reoxidation of the reduced coenzymes (FADH and NADH2) by the transfer of electrons (again in the form of hydrogen) to oxygen, generating H2O (Zubay, 1983, p. 325).

The reduction of oxygen to water to extremely exergonic and most of the ATP is generated during this process. The oxidation of acetyl-CoA involves removal of electrons (as hydrogen) from the Krebs cycle inter-mediates and transfer of hydrogen to the coenzymes FAD and NAD. In the process, these coenzymes are reduced to FADH and NADH2. (In chemistry, “oxi-dation” is the removal of electrons and “reduction” is the addition of electrons.) Subsequently, the reduced coenzymes are reoxidized by transfer of the hydrogens to oxygen in the “electron transport chain.” Ultimate-ly, ATP is synthesized by oxidative phosphorylation of ADP, which is driven by a proton gradient generated in the process of electron transport (Zubay, 1983, p. 325).The reactions of the Krebs cycle can be summarized by the following equation (Zubay, 1983, p. 335):acetyl-CoA + 2 H2O + 3 NAD+ + FAD + ADP + Pi 2 CO2 + 3 NADH + 3 H+ + FADH2 + CoA + ATP Two carbons enter as acetate and exit as CO2, pro-ducing ATP, NADH, and FADH2 as byproducts. The FADH and NADH2 in turn enter the electron transport chain to be further metabolized.Electron Transport and Oxidative PhosphorylationAlthough some ATP is directly generated by the Krebs cycle, more significant products of the cycle are the reduced coenzymes NADH and FADH2. Most of the energy contained in the starting material is still pres-ent in these coenzymes. The primarily energy yield of aerobic metabolism occurs when NADH and FADH2 are re-oxidized to NAD and FAD.

This process is known as electron transport because electrons from NADH and FADH2 are transported via a chain of electron carriers and are ultimately transferred to mo-lecular oxygen.  Oxygen is a very electronegative element, meaning that it has a strong affinity for electrons. In essence, oxygen and hydrogen combine to form water because oxygen has a high affinity for electrons, and hydrogen represents an easy source. Hydrogen does not have a strong affinity for electrons and basically gets trapped into sharing its electrons with oxygen. The overall reactions can be summarized as (Zubay, 1983, p. 364): NADH + H+ + 1/2O2 NAD+ + H20 G = -52.6 kcal/mol FADH2 + 1/2O2 FAD + H20 G = -43.4 kcal/molThe reduced coenzymes NADH and FADH2 serve as donors of electrons (as hydrogen) which combine with oxygen to form water. The delta-G expression indicates that the reaction will proceed spontaneously with the release of energy. Enough energy is released to drive the synthesis of several ATPs. Therefore, rather than wasting energy, the above reaction is di-vided up into several small steps.

The energy release is thus parcelled out in small packets to allow ATP to be generated more efficiently (Zubay, 1983, p. 365).  To achieve this, electrons are transported from the reduced coenzymes to oxygen via a series of carri-ers, arranged in the order of increasing electron affin-ity (figure 2). These electron carriers are molecules (some of them proteins) capable of undergoing revers-ible oxidation-reduction reactions.These electron transporters are embedded within the mitochondrial inner membrane (mitochondria are double-membraned structures). The energy which is released as electrons are transported down the chain to acceptors of ever increasing electron affinity is not directly used to synthesize ATP. Instead, the energy is used to generate a proton gradient across the inner mitochondrial membrane. This results in an electric field across the membrane (about 0.14 V) as well as a pH gradient (about 1.4 units). Protons are actively pumped across the inner mitochondrial membrane us-ing the energy derived from electron transport. In or-der to establish a proton concentration gradient across the membrane, the membrane must be impermeable to passive diffusion of protons.

Protons re-enter the mitochondrial matrix (driven by the concentration gra-dient) through a protein structure embedded within the membrane known as F0. F0 is physically attached to another protein structure known as F1-ATPase, which directly synthesizes ATP from ADP and phosphate. The precise mechanism by which energy is transferred from F0 to F1 and subsequently used to drive ATP synthesis is still under investigation, but may involve protein conformational changes or channeling of pro-tons through the enzyme active site (Zubay, 1983, p. 393). In summary, ATP is a molecule used to transfer energy from fuel substrates to cellular machinery performing work. The specific way in which this is accomplished is simple in principle but complicated in its actual ex-ecution. In principle, energy is derived from foods by their reaction with oxygen, just as when food is burned in a fire. Instead of being released as heat to the sur-roundings, some of the energy is captured as ATP. To achieve this efficiently, the process is broken down into several small steps. The first stage is to convert food molecules into a two-carbon compound, acetyl-CoA. For carbohydrates this is achieved by glycolysis followed by decarboxylation of pyruvate; fatty acids are converted to acetyl-CoA by beta-oxidation.

The acetyl-CoA, whether derived from carbohydrate or fat, is next metabolized in the Krebs cycle. One ATP molecule is generated per acetyl-CoA directly in the Krebs cycle, by “substrate level phosphorylation.” The carbon entering the Krebs cycle is released as CO2. Hydrogen present in the original food is now in the form of the reduced coenzymes NADH or FADH2. Most of the energy from aerobic metabolism is de-rived from oxidation of these reduced coenzymes in the electron transport chain . The summary reactions of the electron transport chain suggest that the hydro-gen from NADH and FADH2 combine with oxygen to form water, a well known exergonic reaction. How-ever, this does not happen directly. Instead, the energy released as electrons are transported down the chain (to electron acceptors of increasing electron affinity) is used to generate a proton gradient across the mito-chondrial membrane. The movement of protons back inside the membrane through the F0-F1 complex pro-vides the driving force for ATP synthesis by F1. This is referred to as “oxidative phosphorylation” because the phosphorylation of ADP to form ATP is coupled to the oxidative events occurring in the electron transport chain .

Energy Production and the AthleteAthletes experience increased energy need as com-pared to sedentary people . Bicycle racers and other endurance athletes can require as much as 10,000 calories per day to support their activity level. Body-builders commonly consume in excess of 8,000 calories daily to fuel their training and support gains in body weight. The body draws on three different types of food as energy substrates: fats, carbohydrates, and protein. Of these, carbohydrate is the most preferred. Carbohydrates are easily digested and rapidly enter the bloodstream as glucose. Glucose is immediately used as fuel by the cell. A byproduct of glucose metabo-lism is malonyl-CoA, which inhibits carnitine acyl-transferase I. Since long chain fatty acids require the carnitine shuttle in order to be transported inside the mitochondria, they are not used as fuel to a significant extent until the carbohydrates are depleted. Similarly, amino acids can be also oxidized to produce energy but are not used as fuel to a significant extent until carbohydrate is depleted. Of course, one of the primary goals of bodybuilders is to increase muscle mass.

Therefore amino acids are more valuable to use as protein rather than as fuel. Conventional fats are not a good energy source for bodybuilders either since they cannot be metabolized anaerobically and are not burned rapidly enough to meet the energy demands of high intensity exercise such as weight lifting (Coleman, 1991). Medium chain triglycerides are absorbed and metabolized much more rapidly than conventional fats and are immediately available for energy (Bach and Babayan, 1982). MCTs are an excellent quick energy source, harnessing the caloric density of fat but being metabo-lized as rapidly as glucose (Bach and Babayan, 1982).  Furthermore, MCTs and the ketone bodies they pro-duce decrease glucose uptake and utilization (Lavau and Hashim, 1978) and this seems to result in a glu-cose-sparing effect (Cotter et al, 1987). MCTs also have a protein-sparing effect and may reduce skeletal muscle protein catabolism, leaving amino acids avail-able for use as protein instead of being oxidized as fuel (Babayan, 1987; Haymond, Nissen, and Miles, 1983). Medium chain triglycerides are an excellent energy source for anyone experiencing increased en-ergy needs (Bach and Babayan, 1982) and are ideally suited to the special needs of athletes.

References

1. Babayan. Medium chain triglycerides and structured lipids. Lipids 22: 417-420 (1987).

2. Bach and Babayan. Medium chain triglycer-ides: an update. Am. J. Clin. Nutr. 36:950-962 (1982).

3. Coleman. Carbohydrates: the master fuel. In: Sports Nutrition for the 90s, eds.Berning and Steen. Aspen Publishers, 1991.

4. Cotter, Taylor, Johnson, and Rowe, A meta-bolic comparison of pure long chain triglyceride lipid emulsion (LCT) and various medium chain tri-glyceride (MCT)-LCT combination emulsions in dogs Am. J. Clin. Nutr. 45: 927-939 (1987).

5. Crozier. Medium chain triglyceride feeding over the long term: the metabolic fate of C-14 octano-ate and C-14 oleate in isolated rat hepato-cytes. J. Nutr. 118: 297-304 (1988).

6. Guyton. Textbook of Medical Physiology. Published by W.B. Saunders, 1976.

7. Haymond, Nissen, and Miles, Effects of ketone bodies on leucine and alanine metabolism in normal man. In: Amino Acids - Metabolism and Medical Applications, Eds. Blackburn, Grant, and Young. Published by John Wright PSG Inc., pages 89-95 (1983).

8. Lavau and Hashim, Effect of medium chain triglyc-eride on lipogenesis and body fat in the rat. J. Nutr. 108: 613-620 (1978).

9. Vander, Sherman, and Luciano. Human Physiology - The Mechanisms of Body Function. Published by McGraw-Hill Book Company, 1980.

10. Zubay. Biochemistry. Addison-Wesley Publishing Company, 1983 .

Parrillo Performance
800-344-3404

First, the fatty acid is converted to its active form, acyl-CoA. The long chain acyl-CoA is then transesterified to L-carnitine by carnitine acyltransferase I (CAT I), generating acylcarnitine. A protein carrier embed-ded within the mito-chondrial membrane acts as a shuttle to transport the LCFA-carnitine complexes into the inner mito-chondrial space . Once there, carnitine acyl-transferase II (CAT II) releases the fatty acid in its activated form, acyl-CoA (figure 1).The enzymes respon-sible for oxidation of fatty acids are located inside the mitochon-dria. Therefore, if fatty acids are not permitted to enter the mitochondria they cannot be burned for energy. Entry into the mitochon-dria is regulated by the activity of the carnitine shuttle. This transport system is not very active if carbohy-drates are available because carbohydrate metabolism generates malonyl-CoA, which inhibits CAT I. In addition, glucagon (the hormonal antagonist of insu-lin) is involved in stimulating mobilization of body fat stores and use of fat for energy. Following carbo-hydrate ingestion insulin is released and glucagon is suppressed, so very little body fat is used for energy.

After carbohydrate reserves have been diminished, the body releases glucagon as a signal to begin burning fat. These are the reasons why fat stores are drawn upon for energy only after glycogen has been depleted.The inhibition of CAT I by malonyl-CoA represents a regulatory mechanism to prevent the wasteful use of energy substrates. Generally speaking, the body uses carbohydrate fuels first and stores fat as an energy reserve. Fat contains twice the energy density of car-bohydrate (9 calories per gram versus 4 calories per gram) and does not require water for storage, as does carbohydrate. Fat is thus a more efficient molecule for energy storage. Ani-mals are able to store only a small amount of energy as carbohydrate (in the form of liver and muscle glycogen) but can store a virtually unlimited amount of energy as fat.In contrast to long chain fats, MCFAs (includes MCTs) are immediately available for energy. Me-dium chain fatty acids are retained by the liver, where they are rapidly and extensively oxidized (Bach and Babayan, 1982). Medium chain fatty acids can en-ter the mitochondria by passive diffusion and do not require the carnitine transport system (Record et al, 1986; Bach and Babayan, 1982).

MCFAs thus can be used for energy even in the presence of carbohydrates, and in fact have a carbohydrate-sparing effect (Lavau and Hashim, 1978; Cotter et al, 1987). Once inside the mitochondria all fatty acids are burned in a process tion. During beta-oxidation, blocks of two carbon atoms are removed from the activated fatty acid (acyl-CoA) to form acetyl-CoA (figure 2). The intermediate acetyl-CoA can then undergo several metabolic fates: i) it can enter the Krebs cycle to generate ATP; ii) it can be used to generate ketone bodies; iii) it can be used as a substrate for fatty acid synthesis or elonga-tion; or iv) it can be consumed in an energy trans-forming process known as reversed electron transfer (Bach and Babayan, 1982; Berry et al, 1985; Crozier et al, 1987).The vast majority of MCFAs (includes MCTs) are re-tained in the liver where they undergo beta-oxidation, producing acetyl-CoA. To enter the Krebs cycle (the body’s central energy producing pathway) the acetyl-CoA combines with oxaloacetate, producing citrate. Me-dium chain fatty acids are oxidized in the liver so rapidly that the supply of oxaloacetate becomes limiting.

As a result, the capacity of the Krebs cycle is overwhelmed and a large proportion of the acetyl-CoA is directed to-ward the synthesis of ketone bodies (Bach and Babayan, 1982). This process is known as “ketogenesis” (figure 3). Ketone bodies are released from the liver into the blood and are subsequebtly taken up by muscles and used as fuel. LCT ingestion also causes an increase in blood levels of ketone bodies during fasting, but only MCT will still produce ketone bodies if carbohydrates are con-currently ingested (Sucher, 1986). Once inside muscle cells, ketone bodies are converted back to acetyl-CoA, which then enters the Krebs cycle to produce ATP. The conversion of MCFAs to ketone bodies occurs even in the presence of carbohydrates. This additional source of energy decreases glucose uptake and utilization (Lavau and Hashim, 1978) and thus may extend endurance by sparing glycogen (Cotter et al, 1987).

References

Bach and Babayan, Medium chain triglycerides: an update. Am. J. Clin. Nutr. 36:950-962 (1982).

Berry, Clark, Grivell, and Wallace, The contribution of hepatic metabolism to diet-induced thermogenesis. Metab. 34: 141-147 (1985).

Cotter, Taylor, Johnson, and Rowe, A metabolic com-parison of pure long chain triglyceride lipid emulsion (LCT) and various medium chain triglyceride (MCT)

LCT combination emulsions in dogs. Am. J. Clin. Nutr. 45: 927-939 (1987).

Crozier, Bois-Joyeux, Chanez, Girard, and Peret, Metabolic effects induced by long-term feeding of medium chain triglycerides in the rat. Metabolism 36: 807-814 (1987).

Lavau and Hashim, Effect of medium chain triglycer-ide on lipogenesis and body fat in the rat. J. Nutr. 108: 613-620 (1978).

Record, Kolpek, and Rapp, Long chain versus medium chain length triglycerides - a review of metabolism and clinical use. Nutr. Clin. Prac. 1:129-135 (1986).

Sucher, Medium chain triglycerides: a review of their enteral use in clinical nutrition. Nutr. Clin. Prac. 44: 146-150 (1986).

Parrillo Performance
800-344-3404

Medium chain triglycerides (MCTs) are comprised of medium chain fatty acids (MCFAs), which are 6-12 carbons in length. Although the carboxylic acid part of fatty acids is soluble in water, the hydrocarbon chain is not. Thus, LCFAs are not water soluble. Since the hydrocarbon chains of MCFAs are shorter, MCFAs are more water soluble than LCFAs. Likewise, MCTs are also relatively soluble in water, due to ionization of the carboxylic acid groups and the small size of the hydrocarbon chains . Their small molecular size and greater water solu-bility cause MCTs to undergo a differ-ent metabolic path than that experienced by LCTs (Bach and Babayan, 1982).

Occurrence and Purification of MCTsMedium chain triglycerides occur naturally in small quantities in a variety of foods, and are present naturally in the blood of the human fetus and in human milk (Bach and Babayan, 1982; Souci, Fachmann, Kraut, 1989/90). In cow’s milk, C6-C14 fatty acids together account for 20% of the total fatty acid composition (Christensen et al, 1989). Commercially, medium chain fatty acids are prepared by the hydrolysis of coconut oil (an abundant source) and are fractionated by steam distillation. The MCFAs so obtained consist of predominantly C8:0, with lesser amounts of C10:0, and minute amounts of C6:0 and C12:0. The fractionated MCFAs are re-esterified with glycerol to generate MCTs (Bach and Babayan, 1982). MCT oil softens or splits certain plastics such as polyethylene and polystyrene, but not polypropylene. It is recommended that MCT oil be stored in metal, glass, or ceramic containers (Sucher, 1986). MCT oil has a caloric density of 8.3 calories per gram; one tablespoon equals 14 grams and contains 115 calories. MCTs are not drugs and have no pharmacological effects (Bach and Babayan, 1982). Historical Uses of MCTsSince their introduc-tion in 1950 for the treatment of fat malab-sorption problems, me-dium chain triglycer-ides have enjoyed wide application in enteral and parenteral nutri-tion regimens (Bach and Babayan, 1982).

Fat emulsions can be used to provide up to 60% of nonprotein calories. Before the availability of lipid emulsions suitable for intravenous use, glucose was used as the only nonprotein source of calories (Mascioli et al, 1987). Not only did this result in essential fatty acid deficiencies, but it was also undesirable because it increased hepatic lipogenesis and respiratory work. Although inclusion of LCTs in intravenous feedings represented an improvement, problems remained with slow clearance of LCTs from the bloodstream and inter-ference with the RES component of the immune system. When medium chain triglycerides or structured lipids (triglycerides containing both MCFAs and LCFAs) are added to the regimen, calories are provided in a more readily oxidizable form (Schmidl, Massaro, and Labuza; 1988), and less interference with the RES is observed (Mascioli et al, 1987). In one case, MCT was fed as the exclusive source of fat (along with a small amount of LCT to provide essential fatty acids) to a patient with chyluria (a fat malabsorption disease) for over 15 years without producing side effects (Geliebter et al, 1983).

Sports NutritionAlthough MCTs have been used in hospital environments for years, their use by healthy individuals is relatively new. Recently, athletes have begun to use MCTs to II. MetabolismDigestion and Absorption of FatsSince LCTs are not very soluble in water, the body has to go through an elaborate digestive process in order to absorb these nutrients. Bile salts are secreted by the gall bladder to help dissolve the LCTs. Upon ingestion, LCTs interact with bile in the duodenum (upper small intes-tine) and are incorporated into mixed micelles (Record et al, 1986). Enzymes called lipases (pancreatic lipase and phospholipase A2) remove the fatty acid molecule from the glycerol backbone. The mixed micelles are passively absorbed into the intestinal mucosa where the free fatty acids are re-esterified with glycerol. The in-testinal mucosa synthesizes a lipoprotein carrier called a chylomicron to transport the reformed triglyceride. Chy-lomicrons are secreted into the lymph and are released into the venous circulation via the thoracic duct. In the bloodstream, lipoprotein lipase again breaks down the triglycerides into two free fatty acids and a monoglyc-eride.

The monoglycerides go to the liver to be further degraded, while many of the circulating free fatty acids are taken up and stored by adipocytes (fat cells). When carbohydrates are consumed insulin is released, and in-sulin stimulates adipocytes to re-esterify the fatty acids into triglycerides and store them as body fat. In general, body fat stores are not mobilized and used for energy to any significant extent in the presence of insulin.In contrast, since MCFAs are more water soluble they are more easily absorbed and do not require this complicated digestive process. MCTs can be absorbed intact and do not require the action of pancreatic lipase or incorpo-ration into chylomicrons. Instead, a lipase within the intestinal cell degrades the MCT into free MCFAs and glycerol. The MCFAs are bound to albumin, released into the bloodstream, and transported directly to the liver by the portal vein. The vast majority of MCFAs are retained by the liver where they are rapidly and extensively oxidized. Whereas conventional fats are largely deposited in fat cells, MCTs are transported directly to the liver and used for energy. Very little of the MCFAs ever escape the liver to reach the general circulation (Bach and Babayan, 1982). Only 1-2% of MCTs are incorporated into depot fat (Geliebter et al, 1983; Baba, Bracco, and Hashim, 1982). Medium chain triglycerides are digested and absorbed much faster than conventional fats (in fact, as rapidly as glucose) and are immediately available for energy.

References

Baba, Bracco, and Hashim, Enhanced thermogenesis and diminished deposition of fat in response to overfeeding with diet containing medium chain triglyceride. Am. J. Clin. Nutr. 35: 678-682 (1982).

Bach and Babayan, Medium chain triglycerides: an up-date. Am. J. Clin. Nutr. 36:950-962 (1982).Christensen, Hagve, Gronn, and Christophersen, Beta-oxidation of medium chain (C8-C14) fatty acids studied in isolated liver cells.

Biochem. et Biophys. Acta 1004: 187-195 (1989).Geliebter, Torbay, Bracco, Hashim, and Van Itallie, Overfeeding with medium chain triglyceride diet results in diminished deposition of fat. Am. J. Clin. Nutr. 37: 1-4 (1983).

Mascioli, Bistrian, Babayan, and Blackburn, Medium chain triglycerides and structured lipids as unique non-glucose energy sources in hyperalimentation . Lipids 22: 421-423 (1987).

Record, Kolpek, and Rapp, Long chain versus medium chain length triglycerides - a review of metabolism and clinical use. Nutr. Clin. Prac. 1:129-135 (1986).

Schmidl, Massaro, and Labuza, Parenteral and enteral food systems. Food Tech. 77-87 (July, 1988).Souci, Fachmann, and Kraut, Food Composi-tion and Nutrition Tables 1989/90. Published by Wissenschaftliche Verlagsgesellschaft (1989).

Sucher, Medium chain triglycerides: a review of their enteral use in clinical nutrition. Nutr. Clin. Prac. 44: 146-150 (1986).Zubay, Biochemistry, chapter 13: “Metabolism of Fatty Acids and Triacylglycerols,” by Denis E. Vance. Published by Addison-Wesley Publishing Company