Subject Pyridoxine

Nutrients and diet supplements without claims of therapeutic effects are considered foods, and are thus regulated by the U.S. Food and Dmg Administration. These are further subject to specific food regulations. Specifications for pyridoxine hydrochloride (7) for foods are given in the Food Chemicals Codex (80) and for pharmaceuticals in the US. Pharmacopeia (81). General test methods have been summarized (82). 

Kratzer (1946) reported that pyridoxine supplementation in chicks on diets containing a linseed meal was necessary to counteract the vitamin B6 deficiency. Klosterman et al. (1967) identified the antipyridoxine factor linatine. Although linatine is a problem in chicks, flaxseed has not been associated with a vitamin B6 deficiency in humans. In fact, no affect on serum pyridoxine levels in subjects consuming 45 grams of flaxseed per day over 5 weeks was observed (Dieken, 1992). 

Although, owing to the wide distribution of vitamin Bg in nature, clinical deficiency symptoms are seldom observed, there is little doubt that pyridoxine is essential in human nutrition. Pyridoxine is absorbed from the gastrointestinal tract and is converted to the active form pyri-doxal phosphate. Absorption is decreased in gastrointestinal diseases and also in subjects taking isoniazid (3). It is excreted in the urine as 4-pyridoxic acid (2). The metabolism of vitamin Bg in human beings has been investigated (56). 

Like glutathione reductase, pyridoxine oxidase is sensitive to riboflavin depletion. In normal subjects and in experimental animals, the EGR and pyridoxine oxidase activation coefficients are correlated, and both reflect riboflavin nutritional status. In subjects with glucose 6-phosphate dehydrogenase deficiency, there is an apparent protection of EGR, so that even in riboflavin deficiency it does not lose its cofactor, and the EGR activation coefficient remains within the normal range. The mechanism of this protection is unknown. In such subjects, the erythrocyte pyridoxine oxidase activation coefficient gives a response that mirrors riboflavin nutritional status (Clements and Anderson, 1980). 

Brown et al. (B25) confirmed the results of Coppini and Camurri (C9) on excretion of kynurenic and xanthurenic acids and, at the same time, examined the excretion of other tryptophan metabolites. Their data indicate that the high levels of all urinary metabolites excreted by pregnant subjects were lowered by pyridoxine administration. It must be remembered that the requirement for pyridoxine in pregnancy varies in the different animal species (C6). It was also found that the levels of pyridoxine in the fetal blood are elevated whereas those of maternal blood decrease (GIO). 

The administration of large doses of pyridoxine (100 mg per day for 30 days) did not change significantly the sum of metabolites excreted by 3 chronie schizophrenic patients after a second load of tryptophan. Only the excretion of 3-hydroxykynurenine is lowered to almost normal levels (B6). Moreover, after a challenging dose of L-tryptophan, chromatographic analysis of the serum of two schizophrenics and one control subject shows that only kynurenine is detectable in blood samples drawn at different intervals of time. 

Auricchio et al. (A12) analyzed the excretory pattern of 6 children with leukemia and 2 with Hodgkin s disease. No definite relationship could be observed between the disease and the abnormally elevated amounts of tryptophan metabolites. After niacin therapy the urinary excretion of kynurenines and kynurenic and xanthurenic acids was normalized in one case of Hodgkin s disease and in one leukemic subject after pyridoxine administration. 

Gershoff and Prien (G6) found that normal subjects excrete significantly less xanthurenic acid and 4-pyridoxic acid and more citric acid than patients with chronic formation of calcium oxalate. A marked rise in excretion of calcium oxalate followed administration of tryptophan in these patients, whereas ingestion of pyridoxine was followed by a decrease in urinary oxalate. 

In subsequent studies (K7), 9 members of 3 different families were loaded with 10 g OL-tryptophan which resulted in a 10-20-fold increase in the 24-hour urinary excretion of kynurenine, 3-hydroxykynurenine, and xanthurenic acid. It appears to be a genetically conditioned disturbance, with dominant inheritance, involving metabolic reactions dependent upon pyridoxine. In most subjects the urinary changes after tryptophan loading could be corrected by vitamin Be therapy. The following diseases were found in this order of frequency in these subjects and their families bronchial asthma, chronic urticaria, anemia, diabetes, arices, and crural ulcers. Knapp s (K7) conclusion is that these disorders may be partially attributable to metabolic disturbances. 

Metabolism of pyridoxine-related compounds in mammals. Enzymes 1, pyridoxal kinase (present in all mammalian tissues) 2, nonspecific (probably alkaline) phosphatases 3, pyridoxine oxidase (cofactor is FMN O2 is required subject to product inhibition) 4, aldehyde oxidase or aldehyde dehydrogenase 5, aminotransferase,... 

Recovery from these symptoms was also facilitated by pyridoxine treatment. Several months after the incident the latter worker developed polyneuritis. The Endings from these studies are limited because the subjects were bum patients. The trauma from the bums may have played a role in some of the neurological effects observed. In addition, pyridoxine is also known to produce neurological effects at high doses, and may have been partially responsible for the delayed polyneuritis. 

Pyridoxine, vitamin B6, (10-50 mg/day) is coadministered with isoniazid to minimize the risk of peripheral neuropathy and central nervous system (CNS) toxicity in malnourished patients and those predisposed to neuropathy (e.g., slow acetylators, elderly, pregnant women, human immunodeficiency virus [HrV]-infected subjects, diabetics, alcoholics, and uremics). 

The use of oral contraceptive agents (OCAs) is widespread and is being increasingly encouraged in developing countries. Their use has been associated with a number of side effects, in particular, a possible increased risk of thrombotic and embolic vascular disease. There is also evidence that OCAs may affect the metabolism of a number of vitamins. Evidence for deficiency of thiamine, riboflb vin, ascorbic acid, pyridoxine, folic acid, and vitamin B12, and for excess accumulation of vitamin A has been reported. This is of particular concern to populations in which vitamin nutrition may already be suboptimal and has been the subject of recent brief reviews (02, R4, Tl, W13). 

Brain, M. C., and Booth, C. C. (1964). The absorption of tritium labelled pyridoxine hydrochloride in control subjects and in patients with intestinal malabsorption. Gut 5,241-247. 

Results of a Loading Test of Ascorbic Acid, Niacinamide, and Pyridoxine in Schizophrenic Subjects and Controls... 

The vitamins were given orally to each patient in a dosage proportional to the two-thirds power of the body weight, with the constant such that a 200-pound subject received 0.01 mole of ascorbic acid and, if the other vitamins were being studied, 0.01 mole of niacinamide and 0.005 mole of pyridoxine. (An exception was the Stanford study, in which for convenience each subject received the 200-pound dose of each... 

Pyridoxine-recovery probability-distribution curves for 44 Stanford control subjects (atove) and for 35 Patton schi2ophrenic subjects (below). 

The pyridoxine distribution functions for the Stanford control group and the Patton patients, calculated in the same way as for ascorbic acid (Figure 2-2), are shown in Figure 2-6. It is seen that there are indications of a division into three groups. The group of low pyridoxine excretors, up to 18 percent (vertical line in Figure 2-6), includes 11 of the 44 Stanford control subjects (25 percent), 1 of the 11 Patton control... 

Results of a loading test of ascorbic acid, niacinamide, and pyridoxine in schizophrenic subjects and controls. In Orthomolecular Psychiatry Treatment of Schizophrenia, David Hawkins and Linus Pauling, eds., W. H. Freeman, San Francisco, (1973), pp. 18-34. (Linus Pauling, Arthur B. Robinson, Susanna S. Oxley, Maida Bergeson, Andrew Harris, Paul Cary, John Blethen, and Ian T. Keaveny. SP 130 ... 

Pyridoxine deficiency has been induced by administration of desoxy-pyridoxine to adults receiving a diet low in B complex vitamins. Seborrheic skin lesions developed about the eyes, nose, and mouth, and cheilosis, glossitis, and stomatitis were observed. Although these findings resemble those commonly seen in riboflavin and niacin deficiency, healing was dependent on administration of pyridoxine. The deficient subjects excreted large amounts of xanthurenic acid in the urine after a test dose of tryptophan, but ability to convert tryptophan to niacin was unimpaired. 

Pyrodoxine has been reported to bring about healing of cheilosis in some subjects. In seborrheic dermatitis of the secca type, application of an ointment containing pyridoxine has been followed by improvement. ... 

Table I summarizes the effects of the various deficiencies of the vitamin B complex upon the response to a variety of antigenic stimuli in different test animals. It is the reviewers opinion that, with the exception of the criticisms already made, this table represents the results of well-controlled, adequate experiments. It is quite apparent that the individual members of the vitamin B complex play a very important role in determining antibody response. Their absence may produce a marked impairment in antibody production. Generalizations on this subject are dangerous, but it would appear that pyridoxine, pantothenic acid, and folic acid deficiencies show the most consistent deleterious effects upon antibody production. It is also apparent that the effects of the individual deficiencies may vary widely depending upon the antigen employed.

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