Drug nutrition interaction

• Drug-nutrient interaction


  The event when a meal, nutrient, or food component affects the way the body processes certain medicines, thus influencing clinical efficacy
• Reasons why drug-nutrient interactions matter

  • Clinical inefficacy
  • Unstable control of symptoms
  • Increased rates of side effects
  • Unexpected adverse events
• Classification of food-drug interactions

  • I. Pharmaceutical (compatibility, solubility, stability)
  • II. Pharmacokinetic (absorption, distribution, metabolism, excretion)
  • III. Pharmacodynamic (clinical effect)
• Classification of food-drug interactions by pre-systemic and post-systemic phases

  • I. Type I (pharmaceutical) = ex vivo bio-inactivations
  • II. Type II = affect the function of an enzyme (type A), a transport mechanism (type B) before systemic circulation altering absorption and bioavailability
  • III. Type III (pharmacokinetic) = after entrance into systemic circulation encompassing changes in tissues distribution, penetration, or metabolism
  • IV. Type IV (pharmacokinetic) = affections in drug or food component clearance because of influences upon renal or enterohepatic excretion
  • V. Type V (pharmacodynamic) = indirect result of previous pharmaceutical or pharmacokinetic interactions or direct interactions with food molecules acting against same drug targets and compete for target-binding
• Pharmaceutical interactions (types I and IIC)

  • The food matrix might directly react with medicines or indirectly alter their absorption by changing the gastrointestinal milieu
• Type I interactions are far more common with drugs and nutrients administered intravenously, as they may be mixed in the delivery device and form precipitates for physical incompatibility
• Type IIC interactions can be considered part of enteral or oral feeding practice, where chelation between divalent and trivalent cations with drugs may occur
• Recommendations to minimize types I and IIC drug-nutrient interactions


  • Drugs should not be mixed directly with feeding enteral or parenteral formulas
  • Tubes should be flushed with water before and after drug administration
  • Preformulated oral solutions or suspensions should be preferred instead of crushing tablets when administering drugs through enteral feeding tubes
  • For drugs with a narrow therapeutic range, monitoring drug levels should be taken into consideration
• Biopharmaceutics Classification System (BCS)

  Classifies drugs according to aqueous solubility and intestinal permeability: class I (high solubility-high permeability), class II (low solubility-high permeability), class III (high solubility-low permeability), class IV (low solubility-low permeability)
• High permeability drugs -which happen to also be food components- are caffeine (coffee, energy drinks, sugary or sugar-free drinks) and theophylline (cocoa, tea)
• The luminal dissolution of a drug product and its transit time, together with its permeability and systemic availability, are greatly affected when the administration occurs shortly after a meal is ingested
• Fed conditions


  The drug product is administered 30 minutes after start of the recommended meal, and with a glass of water. No food is allowed for at least 4 hours post-dose. Water can be allowed as desired except for 1 hour before and after drug administration
• Fasting conditions


  The consumption of the medicine with a glass of water after an overnight fast of at least 10 h. No food is allowed for at least 4 h post-dose, and water intake is allowed as desired except for 1 h before and after drug administration
• Ways food can alter bioavailability of a class II, III, and IV drug

  • Delay of gastric emptying
  • Stimulation of bile flow
  • Change in gastrointestinal pH
  • Increase in splanchnic blood flow
  • Change in luminal metabolism
  • Physical or chemical interaction
• Nutritional bioavailability


  The fraction of ingested food compound that manifests its bioactivity at the biological target
• Major physiological responses and changes in the luminal physicochemical characteristics after meal intake. Data in distal ileum and proximal colon refer to about 5 min after meal intake.
• Food-effect bioavailability (BA) studies

  To assess the effects of food on the rate and extent of absorption of a drug when the drug product is administered shortly after a meal (fed conditions), as compared to administration under fasting conditions
• Fed bioequivalence (BE) studies

  Demonstrate drug bioequivalence to the reference listed drug under fed conditions
• High-energy and high-fat meals (test meals for food-effect studies) are more likely to affect the gastrointestinal physiology and to increase the absorption of hydrophobic drugs through enhanced solubilization. But they can conversely stimulate the formation of drug-bile micelles and decrease hydrophilic drug absorption
• Pharmaceutical

  • Food lipids promote the release of cholecystokinin, which slows gastrointestinal motility and increases the contact time between the drug and the intestinal epithelial tissues (more complete absorption into the portal vein)
  • The content of fat in meals should be accounted for oral chemotherapeutics because of the risk of toxicities
• Pharmaceutical

  • Dietary proteins were found to directly interact with antiepileptic agents (phenytoin) and dopamine precursors (levodopa)
  • Dietary fibre (both soluble and insoluble) may act as a physical barrier and prevent drug contact with the gastrointestinal mucosa, but it can also directly adsorb drug molecules
• Soluble fibres

  Pectin, glucomannan, psyllium, and guar gum are able to form highly viscous solutions in water
• Insoluble components

  Cellulose or bran, create matrices that harness components and increase intestinal transit
• Concomitant alcoholic beverage intake (wine, beer, spirits) is always forbidden, especially for modified-release (MR) systems that could encounter a rapid release known as alcohol-induced dose dumping (ADD)
• Pharmacokinetic interactions

  Happen during the first-pass metabolism of xenobiotics (pre-systemic; first in the intestine and then in the liver after transit in the bloodstream with the stomach accounting for a minor role) and after entrance into the systemic circulation (post-systemic; tissue penetration and metabolism)
• Absorption and excretion mechanisms, together with tissue metabolism, depend on transporters and metabolising enzymes
• Hepatic drug uptake, metabolism, and excretion, are the major determinants of the pre-systemic clearance since liver activity ultimately determines systemic blood levels
• Food-drug interactions that happen after the entry into systemic circulation are part of post-systemic interactions, comprising plasma protein interactions, and have rather similar interferences with proteins or metabolizing enzymes for tissue penetration or metabolism, respectively.
• Influencing factors

  • Patient factors
  • Environmental factors
  • Food factors
  • Drug factors
• Adherence is a multidimensional phenomenon determined by the interplay of five sets of factors, here termed "dimensions", of which patient-related factors are just one determinant.
• The five dimensions of adherence

  • Health care team factors
  • Social/economic factors
  • Condition-related factors
  • Therapy-related factors
  • Patient-related factors
• Patients most likely to have drug-nutrient interactions

  • Fragile individuals (impaired function of the organs involved in drug metabolism)
  • Those on polypharmacotherapy
  • Those not activated
• Fragility

  State of increased vulnerability → decline in reserves and function across multiple physiologic systems, such that the ability to cope with stressors
• Activated patients

  Those with the motivation, knowledge, skills, and confidence to make effective decisions to manage their health
• Body composition alterations (too much fat = hydrophobic drugs accumulate in adipose tissue; fluid balance disturbances)
• Food supplement

  Concentrated source of nutrients (e.g., mineral, vitamins, amino acids, essential fatty acids) or other substances (e.g., herbal extracts) with a nutritional or physiological effect that are marketed in "dose" form (e.g., pills, tablets, capsules, liquids in measured doses)
• Reasons patients use food supplements

  • Feel that they are doing something to help with their own care
  • Help cope with the side effects of treatments, such as nausea, pain, and fatigue
  • Try to treat or cure their symptoms or diseases
  • Comfort themselves and ease the worries of treatment and related stress
• Some drugs interfere with the nutritional status (e.g., nutrient balance, eating behaviors)
• Eating behaviours

  Broad term that encompasses food choice and motives, feeding practices, dieting, and eating-related problems such as obesity, eating disorders, and feeding disorders
• The individual perceives that there is something wrong, and changes eating behaviors and thus food intake