Nutrition and Oral Medicine (Nutrition and Health)

Chapter 6 / Medications, Nutrition, Diet, and Oral Health 89can cause alterations in the absorption of B 12 , folic acid, iron, and the fat-soluble vitamins.Chronic use of medications that decrease the gastric acid can cause B 12 deficiency becausean acidic pH is necessary to free B 12 from its protein-bound state and be available to reactwith intrinsic factor. Iron also requires acidic gastric conditions for optimal absorption,and deficiency can result from reduced gastric acid production. Drugs, such asmetoclopramide, that increase gastric emptying, can cause rapid emptying of food intothe small intestine, which results in reduced nutrients absorption from inadequate timefor gastric digestion or saturation of absorption systems. Mineral oil and overuse oflaxatives can lead to fat-soluble vitamin deficiencies by increasing the rate of intestinalmotility, speeding transit time, and decreasing the amount of time available for nutrientabsorption (8). Increased intestinal motility can also result in inadequate time for potassiumreabsorbtion by the large intestine and can lead to hypokalemia and abnormal heartrhythms.Secondary malabsorption is caused by the interference of a drug with the absorptionor metabolism of another nutrient (9). The primary example are drugs that alter themetabolism of vitamin D, which is responsible for stimulating calcium and phosphorusabsorption to levels that support normal bone mineralization (1). Vitamin D deficiencyleads to inadequate calcium absorption, decreased calcium plasma levels, and reabsorptionof calcium to maintain plasma levels (10). Glucocorticosteroids can cause a loweredproduction of a biologically active vitamin D metabolite, which leads to a consequentdecrease in calcium absorption. They also have a direct action on bone mineralization bycausing mobilization of calcium from the skeleton (1). Demineralization and fracturescan result in steroid-induced osteopenia and osteoporosis with prolonged use (11), especiallyin postmenopausal women. Vitamin D deficiency in patients on chronic anticonvulsantdrugs such as phenobarbital and phenytoin is caused by acceleration at the siteof hepatic conversion of the vitamin and its active metabolite (25-hydroxycholecalciferol)to an inactive form, causing decreased serum calcium levels. Osteomalacia may occurwithin months of the initiation of anticonvulsant therapy, especially in patients withinadequate calcium intakes (12). In both cases, supplemental calcium with vitamin Dshould be provided routinely to avoid such risks.Once absorbed, a nutrient is usually metabolized through enzyme pathways, providinganother opportunity for drugs to interact and affect nutrient metabolism. Drugs canfunction as antivitamins by combining with or inhibiting enzyme systems required for theconversion of vitamins to their coenzyme or active form (1). Often, this interference withthe body’s utilization of a specific nutrient is the desired therapeutic outcome. Folate isnecessary for cells and tissues that rapidly divide, such as cancer cells. Methotrexate, bybinding to dihydrofolate reductase enzyme, prevents the conversion of folic acid (fromdihydrofolate) to its biologically active form (tetrahydrofolate) and inhibits the growthof these cells. Coumarin anticoagulants function as antagonists to vitamin K activity bycausing the retention of the inactive form of vitamin K, thereby inhibiting the coagulationprocess (1). With some drugs, the effect on nutrient metabolism is recognized as anavoidable side effect. Isoniazid and L-dopa both inhibit the normal metabolism of vitaminB 6 , often causing neuropathies that can be reversed with supplements. Anticonvulsants,especially phenytoin and phenobarbital, not only cause vitamin D and K deficiency, butwith prolonged use also cause folic acid deficiency (9) by inducing the liver enzymes thatmetabolize these vitamins.