WaterSoluble Vitamins

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CLINICAL CORRELATION 28.4 Anticonvulsant Drugs and Vitamin Requirements
Anticonvulsant drugs such as phenobarbital or diphenylhydantoin (DPH) present an excellent example of the type of drug–nutrient interactions that are of concern to the physician. Metabolic bone disease appears to be the most significant side effect of prolonged anticonvulsant therapy. Whereas children and adults on these drugs seldom develop rickets or severe osteomalacia, as many as 65% of those on long­term therapy will have abnormally low serum calcium and phosphorus and abnormally high serum alkaline phosphatase. Some bone loss is usually observed in these cases. While the cause of the hypocalcemia and bone loss is thought to be an effect of the anticonvulsant drugs on vitamin D metabolism, not all of the studies have shown decreased levels of 25­(OH)
D and 1,25­(OH)2D in patients on these drugs. However, supplemental vitamin D in the range of 2000–10,000 units per day appears to correct both the hypocalcemia and osteopenia. Anticonvulsants also tend to increase needs for vitamin K, leading to an increased incidence of hemorrhagic disease in infants born to mothers on anticonvulsants. In addition, anticonvulsants appear to increase the need for folic acid and B6. Low serum folate levels are seen in 75% of patients on anticonvulsants and megaloblastic anemia may occur in as many as 50% without supplementation. By bio­chemical parameters, 30–60% of the children on anticonvulsants exhibit some form of B6 deficiency. Clinical symptoms of B6 deficiency are rarely seen, however. From 1 to 5 mg of folic acid and 10 mg of vitamin B6 appear to be sufficient for most patients on anticonvulsants. Since folates may speed up the metabolism of some anticonvulsants, it is important that excess folic acid not be given.
Moslet, U., and Hansen, E. S. A review of vitamin K, epilepsy and pregnancy. Acta Neurol. Scand. 85:39, 1992: Rivery, M. D., and Schottelius, D. D. Phenytoin­folic acid: a review. Drug Intelligence Clin. Pharm. 18:292, 1984; and Tjellesen, L. Metabolism and action of vitamin D in epileptic patients on anticonvulsant treatment and healthy adults. Dan. Med. Bull. 41:139, 1994.
who are prone to poor liver function (reducing preprothrombin synthesis) and fat malabsorption. Clearly, vitamin K deficiency should be suspected in patients demonstrating easy bruising and prolonged clotting time.
28.5— Water­Soluble Vitamins
Water­soluble vitamins differ from fat­soluble vitamins in several important aspects. Most are readily excreted once their concentration surpasses the renal threshold. Thus toxicities are rare. Deficiencies of these vitamins occur relatively quickly on an inadequate diet. Their metabolic stores are labile and depletion can often occur in a matter of weeks or months. Since the water­soluble vitamins are coenzymes for many common biochemical reactions, it is often possible to assay vitamin status by measuring one or more enzyme activities in isolated red blood cells. These assays are especially useful if one measures both the endogenous enzyme activity and the stimulated activity following addition of the active coenzyme derived from that vitamin.
Most of the water­soluble vitamins are converted to coenzymes, which are utilized either in the pathways for energy generation or hematopoiesis. Deficiencies of the energy­releasing vitamins produce a number of overlapping symptoms. In many cases the vitamins participate in so many biochemical reactions that it is impossible to pinpoint the exact biochemical cause of any given symptom. However, it is possible to generalize that because of the central role these vitamins play in energy metabolism, deficiencies show up first in rapidly growing tissues. Typical symptoms include dermatitis, glossitis (swelling and reddening of the tongue), cheilitis at the corners of the lips, and diarrhea. In many cases nervous tissue is also involved due to its high energy demand or specific effects of the vitamin. Some of the common neurological symptoms include peripheral neuropathy (tingling of nerves at the extremities), depression, mental confusion, lack of motor coordination, and malaise. In some cases demyelination and degeneration of nervous tissues also occur. These deficiency symptoms are so common and overlapping that they can be