Role of MCT

Physiology of Fat Digestion and Absorption

Fat absorption is a complex process involving emulsification, enzymatic hydrolysis, and cellular uptake. Unlike proteins and carbohydrates, fats are insoluble in water, requiring specific mechanisms for transport across the aqueous environment of the intestinal lumen and blood.

1. Digestion of Dietary Lipids

The digestion of lipids begins in the mouth and stomach but primarily occurs in the small intestine.

• Lingual and Gastric Lipase Activity

  • Lipid hydrolysis is initiated by lingual lipase and gastric lipase.
  • Lingual lipase activity increases upon sucking, which is particularly relevant for infants.
  • These enzymes are crucial in neonates, especially preterm infants, as they compensate for reduced amounts of pancreatic lipase and bile acids.
  • Gastric lipase contributes to the initial breakdown of triglycerides within the acidic environment of the stomach.

• Emulsification

  • Upon entering the duodenum, fats must be emulsified to increase the surface area for enzymatic action.
  • Bile salts, secreted by the liver and released from the gallbladder mediated by cholecystokinin (CCK), perform a detergent function.
  • Bile salts emulsify fats, breaking large fat globules into smaller droplets.

• Pancreatic Hydrolysis

  • The pancreas secretes pancreatic lipase, which acts on the emulsified fat.
  • Pancreatic lipase hydrolyzes triglycerides into fatty acids and monoglycerides.
  • This process requires colipase (secreted as procolipase) to anchor the lipase to the lipid-water interface.

• Role of Breast Milk Enzymes (in Infants)

  • Human milk contains specific enzymes that aid in fat digestion, including lipoprotein lipase and Bile Salt Stimulated Lipase (BSSL),.
  • BSSL facilitates fat absorption and is capable of hydrolyzing bacterial lipids.
  • BSSL promotes fat absorption in preterm infants who may have pancreatic insufficiency.

2. Absorption into Enterocytes

• Micelle Formation

  • The products of lipolysis (monoglycerides and fatty acids) combine with bile salts to form mixed micelles.
  • Micelles transport these hydrophobic lipids across the unstirred water layer to the brush border of the intestinal epithelial cells.

• Cellular Uptake

  • Fatty acids and monoglycerides detach from the micelles and are absorbed into the intestinal epithelial cells (enterocytes) by diffusion and active transport,.
  • Most nutrient absorption, including fats, occurs in the jejunum and duodenum.

3. Intracellular Processing and Transport

• Re-esterification

  • Once inside the enterocyte, long-chain fatty acids (LCFA) and monoglycerides are reconstituted back into triglycerides.
  • This occurs within the smooth endoplasmic reticulum.

• Chylomicron Formation

  • Reconstituted triglycerides are incorporated into chylomicrons.
  • Chylomicrons are large lipoprotein particles that also contain beta-lipoproteins, cholesterol, and phospholipids.
  • Apolipoprotein B (apoB) is essential for the formation and secretion of chylomicrons,.

• Lymphatic Transport (Long Chain Triglycerides)

  • Chylomicrons are too large to enter the capillaries directly.
  • Instead, they are transported via the lymphatic system into the thoracic duct.
  • From the thoracic duct, they eventually enter the systemic venous circulation.

Medium Chain Triglycerides (MCT)

Medium Chain Triglycerides (MCTs) are a unique class of lipids that are metabolized differently from Long Chain Triglycerides (LCTs). Their distinct absorption pathway makes them a critical tool in clinical nutrition.

Structure and Sources

• Chemical Structure

  • MCTs are composed of fatty acids with carbon chain lengths of 6 to 12 atoms.
  • Specifically, they include caproic (C6), caprylic (C8), capric (C10), and lauric (C12) acids.
  • Sources often define MCTs primarily as C8 and C10 fatty acids.

• Dietary Sources

  • Coconut oil is a rich natural source of MCTs.
  • Palm kernel oil and butter also contain MCTs (butter contains approximately 15% MCT).
  • Unlike LCTs, cereals, pulses, vegetables, and fruits contain negligible amounts of fat.

Metabolism of MCT Absorption

The metabolism of MCTs differs fundamentally from LCTs at the stages of digestion, absorption, and transport.

• Digestion

  • MCTs do not require pancreatic lipase or bile salts for digestion to the same extent as LCTs.
  • They do not require hydrolase for digestion and absorption.

• Absorption and Transport

  • Direct Portal Transport: Unlike LCTs, MCTs are absorbed directly into the portal vein,.
  • Bypassing Lymphatics: MCTs do not require incorporation into chylomicrons or transport through the lymphatic system.
  • Albumin Binding: In the portal blood, Medium Chain Fatty Acids (MCFAs) circulate bound to albumin.

• Hepatic Metabolism

  • Upon reaching the liver via the portal vein, MCTs are metabolized immediately to produce energy.
  • Carnitine Independence: MCTs do not require carnitine for transport across the mitochondrial membrane for oxidation, unlike LCTs which require the carnitine shuttle,.
  • Ketogenesis: MCTs are rapidly oxidized and are ketogenic, readily forming ketone bodies which can serve as an alternative fuel source.

Role of MCT in Nutrition and Therapeutics

Due to their unique absorption and rapid oxidation, MCTs are used extensively in various clinical scenarios, particularly in pediatrics and critical care.

1. Management of Malabsorption Syndromes

MCTs are the preferred fat source when the standard digestive or absorptive mechanisms are compromised.

• Cholestasis and Liver Disease:

  • MCTs are indicated in hepatobiliary diseases because they can be absorbed even when bile flow is decreased,.
  • They are useful in conditions like biliary atresia and neonatal hepatitis where bile salt availability is low.
  • In Lipoprotein Lipase (LPL) deficiency, MCTs are utilized because they bypass the LPL-dependent clearance mechanism required for chylomicrons.

• Pancreatic Insufficiency:

  • MCTs are valuable in the dietary management of cystic fibrosis and other causes of pancreatic insufficiency as they do not strictly require pancreatic lipase for hydrolysis.

• Short Bowel Syndrome:

  • In patients with bowel resection, MCTs provide a concentrated energy source that is easily absorbed, minimizing osmotic load compared to undigested LCTs.

• Intractable Diarrhea:

  • Formulae containing MCTs (e.g., Simyl MCT) are used in severe persistent diarrhea and disaccharide malabsorption.

2. Nutrition for Preterm and Low Birth Weight (LBW) Infants

Preterm infants have immature digestive systems, including reduced bile acid pool size and lower pancreatic lipase activity.

• Fat Absorption:
  • Fat malabsorption and steatorrhea are common in preterms due to these enzymatic deficiencies.
  • MCTs are added to preterm formulas to promote fat absorption because they do not rely on these immature pathways.
• Energy Density:
  • MCTs serve as a dense calorie source to support the rapid growth velocity required in preterms.
  • Coconut oil (rich in MCT) supplements can bridge the calorie gap in malnourished infants.
• Mineral Absorption:
  • MCTs enhance the absorption of calcium and magnesium.
• Nitrogen Sparing:
  • MCTs tend to spare dietary nitrogen, allowing protein to be used for growth rather than energy.

3. Critical Care and Hypermetabolic States

• Protein Sparing Effect:
  • MCTs improve energy provision and spare muscle mass in catabolic states.
• Ketone Production:
  • Ketones produced from MCT oxidation can serve as an alternative fuel for tissues, including the brain.
• Route of Administration:
  • MCTs are included in enteral formulations for critically ill patients.
  • In parenteral nutrition, lipid emulsions may contain a mix of MCT and LCT (usually a 50:50 ratio) to utilize the rapid clearance of MCTs alongside the essential fatty acids of LCTs.

4. Therapeutic Diets

• Ketogenic Diet:

  • MCTs are a core component of the ketogenic diet used for intractable myoclonic seizures.
  • In the MCT-based ketogenic diet, 60% of the fat can be provided as MCT, allowing for more carbohydrate intake compared to classic ketogenic diets while maintaining ketosis.
  • MCTs produce effects by increasing the inhibitory neurotransmitter GABA.

• Sports Nutrition:

  • MCTs are utilized to improve endurance performance and increase metabolic rate.
  • They are marketed as a rapid energy source that spares muscle glycogen stores.

Limitations and Adverse Effects of MCT

While beneficial, the use of MCTs must be balanced and monitored due to specific physiological limitations.

1. Essential Fatty Acid (EFA) Deficiency

• Lack of Linoleic/Linolenic Acid:
  • MCTs do not contain essential fatty acids (linoleic and alpha-linolenic acid).
  • Exclusive use of MCTs as a fat source will lead to EFA deficiency, characterized by cessation of growth, alopecia, dermatitis, and thrombocytopenia,.
• Ratio Requirement:
  • MCTs should ideally be used in combination with Long Chain Triglycerides (LCT) to ensure EFA requirements are met.
  • In preterm formulas, the ESPGAN recommends limiting MCT content to avoid imbalance.

2. Gastrointestinal Intolerance

• Osmotic Diarrhea:
  • Large amounts of MCTs can cause osmotic diarrhea, abdominal distension, and bloating.
  • In preterm infants, excessive MCTs (>40% of fat) may lead to increased gastric aspirates and abdominal distension.
  • Oral administration should be introduced gradually to prevent cramping and nausea.

3. Metabolic Concerns

• Ketosis:
  • Rapid oxidation of MCTs leads to the production of ketone bodies. While therapeutic in epilepsy, uncontrolled ketosis can be detrimental in certain metabolic conditions like acidosis.
  • MCTs are contraindicated in patients with ketotic prone diabetes or specific metabolic defects involving ketone utilization.

Summary of Differences: MCT vs. LCT Absorption

• Digestion: LCTs require pancreatic lipase and bile salts; MCTs do not require these to the same extent.
• Absorption Site: LCTs enter enterocytes via micelles; MCTs diffuse directly.
• Transport Route: LCTs are transported via lymph (chylomicrons); MCTs are transported via the portal vein.
• Carrier Protein: LCTs require lipoproteins (chylomicrons); MCTs bind to albumin in the blood.
• Mitochondrial Entry: LCTs require carnitine shuttle; MCTs enter mitochondria independently of carnitine.