Important Drug-Micronutrient Interactions to Know

Micronutrients and medications use the same transport and metabolic pathways in the body for absorption, metabolism, and elimination.

When a patient is taking medications, there is potential for interaction that may put nutrient balance out of order. Consequently, the action of a drug may also be affected by a micronutrient.

One well-known drug-micronutrient interaction is a decrease in the efficacy of tetracyclines due to calcium. In addition, the physiological function of a vitamin or mineral may be impaired by a drug, such as antagonism of folic acid by methotrexate.

Disturbance of micronutrient levels can result in serious metabolic disturbances, as there is hardly a single physiological process in the body that is not mediated by one or another of these biocatalysts.

Given the ever-increasing number of pharmaceutical products on the market and the frequency with which they are used, greater attention must now be given to the effects of drug therapy on micronutrient balance in order to minimize the potential risk to the health of patients.

When evaluating factors that influence drug-micronutrient interactions, the duration of drug treatment and the patient’s nutritional status prior to the start of treatment are of critical importance. Other factors that need to be taken into account are drug dosage and pharmacokinetic and pharmacodynamics profiles.

A drug has the potential to change many factors depending on its type. Inhibition of endogenous micronutrient synthesis, increased renal/intestinal excretion, impaired absorption of energy sources and micronutrients, and disturbances of micronutrient metabolism are just a few of many examples.

Patient factors influencing micronutrient status include age, sex, illness, dietary habits, self-medication with supplements, gastrointestinal integrity, liver and kidney function, and consumption of unhealthy foods/substances such as alcohol, cigarettes, and candy.

As a general rule, the micronutrient status of a healthy person with a balanced diet is not adversely affected by the use of pharmaceuticals over short periods. If intake of a micronutrient is already inadequate, or if a drug has been taken for a lengthy period or alongside other drugs, then interactions between micronutrients and drugs become relevant and need to be taken into account.

The patient populations that pharmacists should pay the most attention to are the chronically ill on long-term maintenance medications and the elderly with multiple morbidities and multiple drug therapies. Another group of patients are those who are self-medicating without seeking the advice of a physician or pharmacist.

Here is an overview of a selection of common drugs and their interaction with one or more micronutrients, the mechanism of action (MOA) of the interaction, and the consequence of the interaction:

Drug

Micronutrient

MOA

Consequence

Aspirin

Vitamin C

Vitamin E

Iron

Decreased absorption, increased renal excretion, decreased intragastric vitamin C concentration

Interaction with vitamin K at vitamin E dosage ≥800IU/d.

Intensification of irritant action on mucous membranes

Increased gastric mucosa damage

Prolongation of bleeding time

Increased GI intolerability, risk of ulcers

Antacids and acid blockers

Antacids containing Al/Mg hydroxide

Iron/Zinc

pH shift, complex formation

Iron/zinc deficiency

H2 blockers

Vitamin B12

Zinc, Iron

Bacterial colonization, decreased vitamin B12 absorption

pH shift, decreased Zn/Fe absorption

Vitamin B 12 deficiency

Zn/Fe status decreased

Proton pump inhibitors

Vitamin B12

pH shift, decreased absorption, decreased B12 release from R-protein

Vitamin B12 deficiency (megaloplastic anemia), hyperhomocysteinemia

Antiasthmatics

Theophylline

Vitamin B6

Decreased plasma pyridoxal 5-phosphate (PLP) concentration (pyridoxal kinase antagonist)

PLP deficiency (eg, sleep disturbances, nausea, irritability), hyperhomocysteinemia

Antibiotics

Broad-spectrum antibiotics

Biotin, vitamin K

Inhibition of intestinal biotin and vitamin K synthesis

Adverse effect on biotin and vitamin K status

Cephalosporins

Vitamin K

L-Carnitine

Inhibition of endogenous vitamin K synthesis

Renal losses of pivaloylcarnitine, decrease in plasma concentration of free carnitine

Adverse effect on biotin and vitamin K status

Adverse effect on carnitine status

Chloramphenicol

Vitamin B12

Decreased vitamin B12 absorption

Vitamin B12 deficiency (megaloplastic anemia), hyperhomocysteinemia

Tetracyclines

Calcium, magnesium, iron, zinc

Vitamin C

Complex formation, decreased antibiotic absorption

Increased renal vitamin C excretion

Decreased antibiotic efficacy; observe interval between administration

Decreased vitamin C status

Antidiabetics

Oral antidiabetics, insulin

Alpha-lipoic acid

Intensification of the blood sugar-lowering action (increased PDH and alpha-KGDH activity)

Risk of hypoglycemia

Metformin

Vitamin B12

Inhibition of calcium-dependent receptor-mediated endocytosis of the IF-B12 complex (impaired absorption)

Vitamin B12 deficiency (megaloplastic anemia), hyperhomocysteinemia

Antiepileptics

Phenytoin, phenobarbital, primidone, carbamazepine

Vitamin D, calcium

Cytochromes P450 induction, which increases vitamin D metabolism; calcium absorption is decreased and calcium utilization decreased

25-OH-vitD3 and 1,25-(OH)2-VitD3 decreased, PTH increased, pyridinoline increasedàall leading to osteopathia antiepileptica

Phenytoin

Folic acid (Caution: no more than 1 mg folic acid/day)

Increased folic acid metabolism, decreased folic acid absorption, increased oxidative phenytoin metabolism

Folic acid deficiency (increased homocysteine, megaloblastic anemia, gingival hyperplasia); decreased antiepileptic efficacy

Valproic acid

L-Carnitine

Decreased carnitine-acyl-carnitine translocase, increased valproyl-carnitine excretion, decreased carnitine concentration

Carnitine deficiency, cardiac dysfunction, fatigue, liver pathologies

Antihypertensives

ACE inhibitors

Captopril

Candesartan

Potassium

Zinc

Potassium

Renal potassium excretion decreased

Renal zinc excretion increased

Renal potassium excretion decreased

Hyperkalemia

Zinc depletion (e.g.hypogeusia)

Hyperkalemia

Anticoagulants

Vitamin K antagonists

(coumarin)

Vitamin K

Coenzyme Q10

Antagonism

Structural similarity between CoQ10 and Vitamin K

Anticoagulant antagonism

Higher doses of CoQ10 can reduce efficacy of warfarin (monitor INR)

Anti-inflammatories

Diclofenac, Ibuprofen, Indomethacin

Vitamin E

Synergy: inhibition of COX-2 is potentiated by Vitamin E

NSAIDs: anti-inflammatory efficacy increases, requirement decreases, GIT side effects decrease

Methotrexate

Folic acid

Folic acid antagonist (THF reductase)

Folic acid deficiency, leukopenia, thrombocytopenia, stomatitis, gingivitis, hyperhomocysteinemia

Sulfasalazine

Folic Acid

Folic acid absorption decreased

Folic acid deficiency, hyperhomocyseinemia

Antituberculotics

Cycloserine

Vitamin B6

Inactivation of pyridoxal phosphate due to complex formation

Pyridoxal phosphate deficiency, increased neurotoxicity, paresthesias

Ethambutol

Zinc

Complex formation, renal zinc excretion increased

Zinc deficiency, possible disturbances of visual function and optic nerve damage

Isoniazid

Vitamin B6

Inactivation of pyridoxal phosphate due to complex formation (Schiff base)

Vitamin B6 deficiency, increased neurotoxicity, (eg seizures, peripheral neuritis, optic neuritis

Isoniazid, rifampicin

Vitamin D

Vitamin D breakdown due to induction of microsomal liver enzymes

25-OH-D3 concentration decreases, risk of hypocalcemia and hypophosphatemia

Beta blockers

Beta-receptor-blockers

Nicotinic acid (niacin)

Vasodilation increases

Antihypertensive action increased

Bisphosphonates, oral

Alendronate, risedronate

Calcium, Magnesium, Iron, Zinc

Formation of poorly absorbable complexes

Efficacy of bisphosphonates decreased, observe interval of several hours between administration

Corticosteroids

Prednisolone, dexamethasone

Vitamin D, Calcium

Vitamin C

Anti-vitamin D effect: Calcium absorption decreased, renal excretion increased, serum osteocalcin concentration decreased

Vitamin C excretion increased and oxidation increased

Corticoid-induced osteoporosis

Vitamin C status decreased

Diuretics

Thiazides, Furosemide

Thiazides

Furosemide, HCTZ/triamterene

Spironolactone

Magnesium, Potassium

Calcium, Vit D

Folic Acid

Potassium

Mg and K excretion increased, myocardial potassium and magnesium decreased

Renal calcium excretion decreased

Folic acid absorption decreased, renal folic acid excretion increased, folic acid antagonism

Potassium excretion decreased

Vasoconstriction, blood pressure increase, LVEF decrease, (hyperlipidemia, glucose tolerance decreased)

Blood calcium concentration increased

Folic acid status decreased, hyperhomocyseinemia

Hyperkalemia

Antigout drugs

Colchicine

Allopurinol

Vitamin B12

Iron

GI tract: mucosal damage, B12 absorption decreased

Allopurinol can increase iron storage in liver

Vitamin B12 deficiency, megaloblastic anemia

Increased risk of hepatocellular toxicity, combination should be avoided

Updated February 1, 2016