Although vitamin B6 has been shown only recently to be essential in human nutrition, much information has accumulated as to its important role in metabolic processes. Vitamin B8 comprises a group of three closely related compounds, pyridoxine, pyridoxal and pyridoxamine. Pyridoxal phosphate functions as a coenzyme in a number of reactions involving amino acids, namely, decarboxylation, transamination and desulfuration (101). Through these reactions, materials are provided for the Krebs’ cycle, which is one of the important energy sources of the body, new amino acids are formed and sulfhydryl groups are transferred from one compound to another. Vitamin B6 has a role in tryptophan metabolism in the conversion of tryptophan to niacin derivatives and functions in the interconversion of essential fatty acids. The exact requirement of vitamin B6 has not been determined but available evidence suggests that 1.0 to 2.0 mg. daily should be sufficient for an adult, an amount easily provided by the average diet in the United States.
Vitamin B6 Deficiency
Vitamin B6, deficiency was induced experimentally in two infants both of whom ceased gaining weight, while one developed convulsions and the other hypochromic anemia (102). Pyridoxic acid, the main excretory product of pyridoxine metabolism, disappeared from the urine and the ability to convert tryptophan to niacin was lost. A syndrome apparently due to vitamin B6 deficiency was observed in infants who received a proprietary liquid milk formula (103). Findings included irritability, easy startling, abdominal distention, muscular twitchings and convulsive seizures. The electroencephalogram was abnormal in several instances. Recovery followed a change of formula or administration of a large amount of pyridoxine. Investigation indicated that the sterilization process had destroyed some of the vitamin B6 in this milk preparation. There had also been some change in the fatty acid composition of the mixture. As a result of this unfortunate episode, some knowledge of vitamin B6 requirement was obtained. Symptoms developed in infants who received 60 micrograms of vitamins B6 per liter of milk while none occurred in infants fed 100 pg. of vita-man B6 per liter.
Several attempts have been made to induce vitamin B6 deficiency in adults (101). In one experiment, in which two subjects were maintained on a vitamin B6-deficient diet for three weeks, excretion of xanthurenic acid after ingestion of tryptophan was increased (104). Xanthurenic acid is an abnormal product of tryptophan metabolism which appears in the urine in vitamin B6 deficiency. In another experiment, one subject was maintained on a vitamin B6-deficient diet for 54 days without developing any manifestations of deficiency disease. Vilter and associates (105) studied the problem of vitamin B6 deficiency by administering a pyridoxine antagonist, desoxypyridoxine, to adults, some of whom also received a diet low in B complex vitamins. Many of the patients became irritable, depressed and sometimes somnolent. Seborrheic dermatitis developed about the eyes, in the nasolabial folds and in the eyebrows and spread to involve the face, forehead, chin, up into the hair and down the neck. Occasionally, hyperpigmented, scaling, pellagrous-like dermatitis developed on the arms and legs. Cheilosis, glossitis, angular stomatitis, peripheral neuritis and conjunctivitis were noted in some subjects. These lesions, many of which resemble those of riboflavin, thiamine or niacin deficiency, healed only after pyridoxine was ad-ministered. Lymphopenia occurred regularly in these subjects. The excretion of xanthurenic acid in the urine after administration of a test dose of tryptophan was markedly increased but the conversion of tryptophan to niacin was unimpaired. Abnormally high levels of blood urea nitrogen were observed after administration of alanine.
Several studies indicate that pyridoxine metabolism may be altered during pregnancy. Lower levels of urea nitrogen in the blood were found in pregnant than in nonpregnant women and concentrations were still further reduced in hyperemesis gravidarum. When the amino acid alanine was administered, blood urea nitrogen concentration remained elevated for more than 12 hours. Similar findings have been reported in vitamin B6 deficiency in animals. Pregnant women have been found to excrete abnormally large amounts of xanthurenic acid after administration of tryptophan, the abnormality being corrected by pyridoxine . These findings suggest that pyridoxine requirement may be increased during pregnancy.
Large amounts of pyridoxine have been shown to pre-vent or alleviate the peripheral neuritis which may develop during therapy with isoniazid. It has been hypothesized that isoniazid may couple with pyridoxal to form pyridoxal isoniazid hydrozone thus inactivating enzyme systems dependent on pyridoxal. In this way, a conditioned vitamin B6 deficiency might be induced. The peripheral neuritis which has been observed in some subjects with chronic alcoholism has improved following pyridoxine administration. In some instances, xanthurenic acid excretion after tryptophan administration was abnormally high prior to treatment and decreased following pyridoxine administration. Pyridoxine has been used in the treatment of cheilosis, the lesions healing in some subjects. In seborrheic dermatitis of the secca type, application of an ointment containing pyridoxine, but not oral administration of the vitamin, resulted in improvement in lesions in one series of subjects but not in another (101).
Although dietary deficiency of pyridoxine is an unlikely possibility, it seems logical to anticipate that deficiency may occur in numerous situations in which metabolism is deranged. The appearance of some of the clinical manifestations enumerated above should stimulate diagnostic studies to evaluate pyridoxine nutrition. Two laboratory procedures are available which measure metabolic functions of pyridoxine. Administration of a large dose, 10.0 gm., of dl-tryptophan stresses the enzyme systems responsible for its degradation. Normal subjects will excrete less than 50.0 mg. of xanthurenic acid in the urine in the 24 hours after this test dose, while subjects with deficiency will excrete larger amounts. The second procedure is determination of the concentration of blood urea nitrogen after administration of 30.0 gm. of alanine. The concentration should return to normal within twelve hours if pyridoxine is available in adequate amounts.