Folic acid supplementation can partially reverse the hematologic abnormalities of B12 deficiency and, therefore, can mask a cobalamin deficiency. Thus, to prevent the later CNS effects of B12 deficiency, therapy for megaloblastic anemia is initiated with both vitamin B12 and folic acid until the cause of the anemia can be determined.
IV. ASCORBIC ACID (VITAMIN C)
The active form of vitamin C is ascorbic acid (Fig. 28.8). Its main function is as a reducing agent. Vitamin C is a coenzyme in hydroxylation reactions (for example, hydroxylation of prolyl and lysyl residues in collagen; see p. 47), where its role is to keep the iron (Fe) of hydroxylases in the reduced, ferrous (Fe+2) form. Thus, vitamin C is required for the maintenance of normal connective tissue as well as for wound healing. Vitamin C also facilitates the absorption of dietary nonheme iron from the intestine by reduction of the ferric form (Fe+3) to Fe+2 (see p. 403).
A. Deficiency
Ascorbic acid deficiency results in scurvy, a disease characterized by sore and spongy gums, loose teeth, fragile blood vessels, hemorrhage, swollen joints, bone changes, and fatigue (Fig. 28.9). Many of the deficiency symptoms can be explained by the decreased hydroxylation of collagen, resulting in defective connective tissue. A microcytic anemia caused by decreased absorption of iron may also be seen.
B. Chronic disease prevention
Vitamin C is one of a group of nutrients that includes vitamin E (see p. 395) and β-carotene (see p. 386), which are known as antioxidants. [Note: Vitamin C regenerates the functional, reduced form of vitamin E.] Consumption of diets rich in these compounds is associated with a decreased incidence of some chronic diseases, such as cardiovascular disease (CVD) and certain cancers. However, clinical trials involving supplementation with the isolated antioxidants have failed to demonstrate any convincing preventive effects.
V. PYRIDOXINE (VITAMIN B6)
Vitamin B6 is a collective term for pyridoxine, pyridoxal, and pyridoxamine, all derivatives of pyridine. They differ only in the nature of the functional group attached to the ring (Fig. 28.10). Pyridoxine occurs primarily in plants, whereas pyridoxal and pyridoxamine are found in foods obtained from animals. All three compounds can serve as precursors of the biologically active coenzyme, pyridoxal phosphate (PLP). PLP functions as a coenzyme for a large number of enzymes, particularly those that catalyze reactions involving amino acids, for example, in the transsulfuration of Hcy to cysteine (see p. 264). [Note: PLP is also required by glycogen phosphorylase (see p. 128).]
A. Clinical indications for pyridoxine
Isoniazid, a drug commonly used to treat tuberculosis, can induce a vitamin B6 deficiency by forming an inactive derivative with PLP. Thus, dietary supplementation with B6 is an adjunct to isoniazid treatment. Otherwise, dietary deficiencies in pyridoxine are rare but have been observed in newborn infants fed formulas low in B6, in women taking oral contraceptives, and in those with alcoholism.
B. Toxicity