Micronutrients in Health and Disease: Drug–Diet Interactions

Drug–diet interactions can cause increased needs for certain micronutrients. Electrolyte imbalances are probably the most common micronutrient deficiency states, and are often caused by medications.¹³

Folic acid deficiency may occur due to treatment with many anticonvulsants (eg, phenytoin, carbamazepine, phenobarbital, valproic acid), and may subsequently increase the risk for birth defects.⁵³ Through an antagonizing effect on folate, these same drugs also significantly increase certain indicators of cardiovascular risk, such as homocysteine and possibly lipoprotein(a).⁵⁴ Available data indicate that folic acid treatment can significantly reduce homocysteine in children on anticonvulsant medications.⁵⁵ Additional studies are needed to test the initial observation that B–vitamin supplements (folate, pyridoxine, and riboflavin) reduce certain other cardiovascular risk factors, including von Willebrand factor and lipoprotein, that are elevated in adults on anticonvulsant treatment.⁵⁶

Many side effects of methotrexate treatment (gastro–intestinal intolerance, stomatitis, alopecia, and cytopenia) are due to folate antagonism. However, it is thought that these effects may be avoided by combining a folate–rich diet with minimal folate supplementation (ie, multiple vitamins) and by reducing the dose of methotrexate if necessary.⁵⁷ American College of Rheumatology guidelines indicate that supplementation with additional folic acid or folinic acid (Leucovorin) may prevent treatment side effects without compromising therapeutic efficacy.58 Although doses of 2.5 mg to 5.0 mg reduce the side effects of methotrexate without significantly altering effectiveness, higher amounts (eg, 15 mg) have resulted in worsening of rheumatoid arthritis (RA) symptoms.⁵¹

Vitamin B₁₂ absorption decreases as a result of long–term acid suppression therapy (eg, proton pump inhibitors) and can exacerbate the already–declining absorption of this vitamin caused by atrophic gastritis.⁵⁹ Long–term treatment with metformin also decreases B₁₂ absorption,⁶⁰ apparently as a result of inhibiting a calcium–dependent process that normally promotes ileal uptake of the B₁₂–intrinsic factor complex. Preliminary data indicate that this effect is ameliorated by calcium supplementation.⁶¹

Hypokalemia frequently results from commonly used diuretics, amphotericin B, corticosteroids, antipseudomonal penicillins, and insulin, while hyperkalemia may result from heparin,¹³ as well as potassium–sparing diuretics and poor kidney function.⁶²

Hypomagnesemia and thiamine deficiencies frequently result from treatment with diuretics, and the former can also occur due to administration of amphotericin B, aminoglycoside antibiotics, and cyclosporine.^13,26 Cisplatin therapy may cause hypomagnesemia.⁶³

Hypocalcemia may result from foscarnet by forming a complex with ionized calcium.¹³ It may also occur in patients given bisphosphonates who have unrecognized hypoparathyroidism, impaired renal function, or vitamin D deficiency.⁶⁴

Sodium imbalances may occur due to the ubiquitous presence of sodium and phosphorus in foods; deficiencies of these electrolytes are less common. Hyponatremia, however, can occur from carbamazepine and thiazide diuretics, while hypernatremia can result from drugs that cause diarrhea (eg, lactulose).

Hypophosphatemia may result from the use of antacids or sucralfate.