Fructose

Fructose is a naturally occurring monosaccharide used primarily in clinical settings as an energy source or for the management of specific metabolic conditions.

Approved Indications:

• Hypoglycemia: Rapid correction of symptomatic hypoglycemia, particularly in patients unable to ingest oral glucose.
• Parenteral Nutrition: Component of intravenous nutrition solutions to provide caloric support.
• Hereditary Fructose Intolerance (HFI): Diagnostic testing under controlled conditions; used cautiously as part of metabolic evaluation.

Off-label / Clinically Accepted Uses:

• Energy Supplementation: For patients with glycogen storage diseases or other metabolic disorders requiring rapid carbohydrate availability.
• Cardiac Stress Testing: Intravenous fructose may be used in experimental or research protocols as a substrate in metabolic studies.
• Oral Nutritional Support: In certain cases of malnutrition or limited carbohydrate tolerance.

Adults:

• IV Administration: 0.5–1 g/kg as a slow infusion; adjust according to blood glucose monitoring and clinical response.
• Oral Administration: 25–50 g per dose, depending on dietary needs; often included in enteral formulations.

Pediatrics:

• IV: 0.25–0.75 g/kg per dose, titrated to effect; frequent glucose monitoring recommended.
• Oral: Dosing varies with age and weight; usually incorporated into pediatric nutritional solutions.

Special Populations:

• Renal Impairment: Monitor for fluid overload and electrolyte imbalance; adjust infusion rates.
• Hepatic Impairment: Use caution in patients with fructose intolerance or impaired hepatic metabolism.

Administration Routes:

• Oral, intravenous (IV) infusion.
• IV route preferred in acute hypoglycemia or when oral intake is not feasible.

Fructose is metabolized primarily in the liver through the fructolysis pathway. It is phosphorylated by fructokinase to fructose-1-phosphate, bypassing the regulatory step of phosphofructokinase in glycolysis. This results in rapid generation of triose phosphates, which enter glycolysis to produce ATP. The rapid availability of energy substrates helps correct hypoglycemia and supports cellular metabolism in energy-demanding states.

• Absorption: Rapidly absorbed from the gastrointestinal tract when administered orally.
• Distribution: Distributes in total body water; freely crosses cellular membranes via GLUT5 transporters.
• Metabolism: Primarily hepatic via fructokinase to fructose-1-phosphate; further metabolized to glyceraldehyde and dihydroxyacetone phosphate.
• Half-life: Very short; rapidly cleared through hepatic metabolism.
• Excretion: Minimal unchanged fructose in urine; metabolites enter gluconeogenesis or glycolysis pathways.
• Onset of Action: Oral fructose raises blood glucose within 10–20 minutes; IV administration is immediate.

• Pregnancy: Fructose is generally considered safe as a nutrient source; excessive intake should be avoided.
• Lactation: Safe for breastfeeding; fructose naturally occurs in breast milk.
• Caution: In mothers with hereditary fructose intolerance, dietary monitoring is required.

• Primary Class: Carbohydrate / Nutritional supplement
• Subclass: Monosaccharide

• Known hereditary fructose intolerance.
• Severe hepatic impairment preventing fructose metabolism.
• Hypersensitivity to fructose-containing formulations.

• Metabolic Disorders: Use caution in patients with diabetes mellitus; monitor blood glucose.
• Renal Impairment: Risk of fluid overload with IV administration.
• Electrolyte Imbalance: Monitor serum electrolytes during prolonged IV infusion.
• Obesity / Hypertriglyceridemia: Excessive intake may exacerbate metabolic conditions.

Common:

• Mild gastrointestinal discomfort, bloating, or diarrhea with oral administration.
• Hyperglycemia if used excessively.

Serious / Rare:

• Hepatic dysfunction in patients with underlying metabolic disorders.
• Exacerbation of lactic acidosis in rare metabolic conditions.
• Rare allergic reactions to formulation excipients.

Timing & Severity:

• GI effects typically occur within 1–2 hours of oral ingestion.
• IV administration adverse effects are rare if infusion rate and glucose monitoring are appropriate.

• Insulin or Antidiabetic Agents: Risk of hyperglycemia if combined; monitor glucose.
• Other Parenteral Nutrition Components: Electrolyte and osmolarity interactions may occur; adjust formulation.
• Alcohol: Excessive consumption may increase hepatic metabolic load.

• Fructose remains recommended as a rapid energy source in hypoglycemia unresponsive to oral glucose.
• Recent guidelines highlight cautious use in hereditary fructose intolerance and other metabolic disorders.
• Parenteral nutrition protocols emphasize controlled infusion rates to avoid hyperglycemia or electrolyte disturbances.

• Store at 20°C to 25°C (room temperature).
• Protect from light and moisture.
• Use sterile techniques for IV administration.
• Oral formulations should be kept in tightly sealed containers; avoid excessive heat or humidity.