🍎Medical Nutrition Therapy I Unit 14 – Drug-Nutrient and Food-Drug Interactions

Key Concepts and Definitions

• Drug-nutrient interactions occur when a drug affects the absorption, metabolism, or excretion of a nutrient or when a nutrient affects the absorption, metabolism, or effectiveness of a drug
• Food-drug interactions happen when food components (nutrients, phytochemicals, or other substances) alter the pharmacokinetics or pharmacodynamics of a drug
• Pharmacokinetics refers to the processes of drug absorption, distribution, metabolism, and excretion (ADME) in the body
• Pharmacodynamics describes the biochemical and physiological effects of drugs on the body, including the mechanisms of drug action and the relationship between drug concentration and effect
• Bioavailability is the fraction of an administered dose of a drug that reaches the systemic circulation and is available at the site of action
• Cytochrome P450 (CYP) enzymes are a superfamily of heme-containing enzymes involved in the metabolism of many drugs, nutrients, and endogenous compounds
  • CYP3A4 is the most abundant CYP enzyme in the human liver and intestine and is responsible for metabolizing a wide range of drugs (statins, calcium channel blockers, immunosuppressants)
• P-glycoprotein (P-gp) is an ATP-dependent efflux transporter that pumps various substrates, including drugs and nutrients, out of cells and plays a crucial role in drug absorption and distribution

Mechanisms of Drug-Nutrient Interactions

• Altered gastrointestinal pH can affect drug absorption by influencing drug solubility and ionization (antacids, proton pump inhibitors)
• Formation of insoluble complexes between drugs and nutrients can reduce drug absorption (tetracyclines and calcium, iron, or magnesium)
• Competition for transport proteins can occur when drugs and nutrients share the same uptake or efflux transporters (P-gp, organic anion transporting polypeptides)
• Induction or inhibition of drug-metabolizing enzymes by nutrients can alter drug metabolism and clearance
  • Grapefruit juice inhibits CYP3A4, leading to increased bioavailability of certain drugs (felodipine, simvastatin)
  • Cruciferous vegetables (broccoli, Brussels sprouts) induce CYP1A2, potentially reducing the effectiveness of some drugs (clozapine, olanzapine)
• Altered renal excretion of drugs or nutrients can result from changes in urinary pH or competition for renal tubular transport systems (probenecid and penicillins)
• Synergistic or antagonistic pharmacodynamic interactions can occur when drugs and nutrients have similar or opposing effects on the same biological target or pathway (vitamin K and warfarin)

Common Food-Drug Interactions

• Grapefruit juice inhibits CYP3A4, increasing the bioavailability of certain drugs (calcium channel blockers, statins, immunosuppressants)
• Tyramine-containing foods (aged cheeses, cured meats, soy sauce) can cause hypertensive crisis when consumed with monoamine oxidase inhibitors (MAOIs)
• Vitamin K-rich foods (green leafy vegetables, soybean oil) can antagonize the anticoagulant effects of warfarin
• High-fiber diets can reduce the absorption of various drugs (digoxin, levothyroxine) by adsorption or increased gastrointestinal motility
• Calcium-rich foods or supplements can decrease the absorption of certain antibiotics (tetracyclines, fluoroquinolones) by forming insoluble complexes
• Alcohol can enhance the sedative effects of central nervous system depressants (benzodiazepines, opioids) and increase the risk of gastrointestinal bleeding with nonsteroidal anti-inflammatory drugs (NSAIDs)
• Caffeine can antagonize the effects of adenosine receptor agonists (dipyridamole) used in cardiac stress tests

Nutritional Implications of Medications

• Antacids and proton pump inhibitors can reduce the absorption of vitamin B12, iron, and calcium by altering gastrointestinal pH
• Metformin, a common diabetes medication, can cause vitamin B12 deficiency by impairing its absorption in the terminal ileum
• Corticosteroids can lead to bone loss and increased risk of osteoporosis by reducing calcium absorption and increasing renal calcium excretion
• Certain antibiotics (tetracyclines, fluoroquinolones) can chelate with minerals (calcium, iron, zinc), reducing their absorption and bioavailability
• Cholestyramine, a bile acid sequestrant used to treat hypercholesterolemia, can impair the absorption of fat-soluble vitamins (A, D, E, K)
• Valproic acid, an anticonvulsant, can interfere with carnitine metabolism and cause carnitine deficiency, affecting energy production and fatty acid oxidation
• Isoniazid, an antituberculosis drug, can cause vitamin B6 deficiency by forming inactive complexes with pyridoxal phosphate, the active form of vitamin B6

Clinical Assessment and Monitoring

• Obtain a comprehensive medication history, including prescription drugs, over-the-counter medications, herbal supplements, and dietary habits
• Assess nutritional status using anthropometric measurements (weight, height, BMI), biochemical markers (serum albumin, prealbumin, transferrin), and clinical signs and symptoms of nutrient deficiencies
• Monitor therapeutic drug levels and adjust dosages as needed, considering potential drug-nutrient interactions
  • Examples include monitoring INR (international normalized ratio) for patients on warfarin and vitamin K intake, or monitoring serum digoxin levels in patients with concomitant use of high-fiber diets
• Evaluate renal and hepatic function to identify patients at higher risk for drug-nutrient interactions due to impaired drug metabolism or excretion
• Consider pharmacogenetic testing to identify genetic variations in drug-metabolizing enzymes (CYP2C9, CYP2D6) that may affect drug response and susceptibility to drug-nutrient interactions
• Collaborate with healthcare providers (physicians, pharmacists, nurses) to optimize drug therapy and minimize adverse drug-nutrient interactions

Dietary Strategies for Managing Interactions

• Adjust timing of drug administration in relation to meals to minimize interactions
  • Take certain medications (tetracyclines, fluoroquinolones) at least 2 hours before or 6 hours after consuming calcium-rich foods or supplements
  • Administer levothyroxine on an empty stomach, 30-60 minutes before breakfast, to enhance absorption
• Recommend alternative medications with lower interaction potential when possible (enalapril instead of captopril for patients on high-potassium diets)
• Modify diet composition to minimize interactions while ensuring adequate nutrient intake
  • Limit grapefruit juice consumption in patients taking CYP3A4-metabolized drugs
  • Encourage consistent vitamin K intake in patients on warfarin therapy to maintain stable INR values
• Supplement with specific nutrients when medications interfere with their absorption or metabolism (vitamin B12 supplementation with metformin use, calcium and vitamin D supplementation with corticosteroid therapy)
• Monitor and adjust nutrient intake based on clinical response and laboratory values (serum vitamin B12, 25-hydroxyvitamin D, INR)
• Educate patients on the importance of maintaining a balanced diet and the potential consequences of restrictive diets on medication effectiveness and nutrient status

Patient Education and Counseling

• Provide clear, easy-to-understand information about potential drug-nutrient interactions and their consequences
• Emphasize the importance of disclosing all medications, supplements, and herbal products to healthcare providers to identify and manage interactions
• Teach patients how to read medication labels and recognize potential interactions with food or nutrients
• Offer practical strategies for managing drug-nutrient interactions, such as adjusting medication timing, modifying diet composition, or using reminder systems
• Encourage patients to communicate any concerns or adverse effects related to drug-nutrient interactions to their healthcare providers
• Provide resources (handouts, websites, support groups) for patients to learn more about their medications and the role of nutrition in their health
• Emphasize the importance of regular follow-up visits to monitor therapeutic response, adverse effects, and nutritional status

Case Studies and Practical Applications

• A 65-year-old woman with hypertension and osteoporosis is prescribed a thiazide diuretic and calcium supplements. The registered dietitian recommends taking the calcium supplements at least 2 hours apart from the thiazide diuretic to minimize the risk of hypercalcemia and kidney stones.
• A 45-year-old man with HIV is on antiretroviral therapy, including a protease inhibitor (ritonavir). The registered dietitian advises the patient to avoid consuming large amounts of garlic or taking garlic supplements, as garlic can induce CYP3A4 and reduce the effectiveness of ritonavir.
• A 30-year-old woman with epilepsy is treated with phenytoin, an anticonvulsant that interferes with vitamin D metabolism. The registered dietitian recommends vitamin D supplementation and regular monitoring of serum 25-hydroxyvitamin D levels to prevent osteomalacia and fractures.
• A 55-year-old man with type 2 diabetes is prescribed metformin and reports symptoms of peripheral neuropathy. The registered dietitian suspects vitamin B12 deficiency and recommends testing serum B12 levels and considering B12 supplementation if deficiency is confirmed.
• A 75-year-old man with atrial fibrillation is on warfarin therapy and reports a significant increase in his consumption of green leafy vegetables. The registered dietitian educates the patient on the importance of maintaining consistent vitamin K intake and communicating any dietary changes to his anticoagulation clinic to ensure stable INR control.