High Doses of Vitamin B<sub>6</sub> in the Rat Are Associated with Inhibition of Hepatic Tryptophan Metabolism and Increased Uptake of Tryptophan into the Brain

Bender, David A.; Totoe, Lena

doi:10.1111/j.1471-4159.1984.tb12793.x

Cited by 15 publications

(4 citation statements)

References 21 publications

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“…It is noteworthy that after the relatively high dose of pyridoxine hydrochloride given to the animals there was a reduction in metabolic flux through tryptophan dioxygenase, as shown by decreased formation of 14 CO 2 from [nng-2-14 C]tryptophan, and consequently reduced formation of 14 CO 2 from [methylene-14 C]tryptophan. This has been reported previously in rats (Bender & Totoe, 1984), and is believed to reflect attenuation of the nuclear actions of glucocorticoid hormones in response to high intracellular concentrations of pyridoxal phosphate -the reverse of the enhanced responsiveness to steroid hormones which is seen in vitamin B 6 deficiency (Bender, 1987).…”

Section: Discussionsupporting

confidence: 67%

Tryptophan metabolism and vitamin B₆nutritional status in patients with schistosomiasis mansoni and in infected mice

1992

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Patients infected with Schistosoma mansoni showed an abnormal response to a test dose of tryptophan, with little increase in the urinary excretion of kynurenine, hydroxykynurenine, xanthurenic and kynurenic acids, N1-methyl nicotinamide, methyl pyridone carboxamide, 5-hydroxytryptamine or 5-hydroxyindoleacetic acid. In contrast to previous reports, this is different from the pattern of tryptophan metabolism seen in vitamin B6 deficiency. Furthermore, the patients' plasma concentrations of pyridoxal phosphate were within the reference range, and supplementation for 5 days with 20 mg vitamin B6/day did not affect tryptophan metabolism. Treatment with a single dose of Praziquantel resulted in a substantial restoration of normal tryptophan metabolism. In mice infected with S. mansoni there was a similar impairment of tryptophan metabolism, as shown by considerably reduced formation of 14CO2 after the administration of a tracer dose of [14C]tryptophan. Again, the administration of vitamin B6 supplements did not correct tryptophan metabolism in the mice. Treatment with Praziquantel resulted in substantial restoration of the production of 14CO2 from [14C]tryptophan. There was no evidence of vitamin B6 deficiency (as determined by erythrocyte aspartate aminotransferase activation coefficient) associated with infection in the mice, although there was a redistribution of pyridoxal phosphate between tissues, with a reduction in the concentration of liver, spleen and kidney, and an increase in skeletal muscle.

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Section: Discussionsupporting

confidence: 67%

Tryptophan metabolism and vitamin B₆nutritional status in patients with schistosomiasis mansoni and in infected mice

1992

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“…It is unlikely that this explains the differential effect of vitamin B 6 deficiency on serotonin and catecholamine formation, since the inactivation is the result of a covalent modification of the catalytic site, not the coenzyme, and is not reversed by incubation with PLP (Bertoldi et al 1996). Bender & Totoe (1984b) showed that in rats high doses of vitamin B 6 (10 mg/kg body weight) led to decreased oxidative metabolism of tryptophan, an increased plasma concentration of tryptophan, and increased uptake of tryptophan into the brain, leading to an increased rate of serotonin turnover. They suggested that vitamin B 6 supplements might be a useful adjunct to tryptophan for the treatment of depression.…”

Section: Depressionmentioning

confidence: 99%

Non-nutritional uses of vitamin B₆

Bender

1999

Br J Nutr

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101

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Vitamin B6is a water-soluble vitamin, and is readily metabolized and excreted, so it has generally been assumed to have negligible toxicity, although at very high levels of intake it can cause peripheral nerve damage. Nutritional deficiency disease is extremely rare, although a significant proportion of the population shows biochemical evidence of inadequate status, despite apparently adequate levels of intake. The vitamin has been used to treat a wide variety of conditions, which may or may not be related to inadequate intake. In some conditions use of vitamin B6supplements has been purely empirical; in other conditions there is a reasonable physiological or metabolic mechanism to explain why supplements of the vitamin many times greater than average requirements may have therapeutic uses. However, even in such conditions there is little evidence of efficacy from properly conducted controlled trials.

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“…45 There is some evidence that tryptophan has a useful antidepressant action, albeit with a narrow therapeutic window, because at relatively high concentrations, it stabilizes tryptophan dioxygenase and so increases the rate at which it undergoes oxidative metabolism rather than hydroxylation and decarboxylation to yield serotonin. 46 As discussed above, pyridoxal phosphate acts to terminate the actions of steroid hormones, and tryptophan dioxygenase is induced by glucocorticoid hormones. In rats, a relatively high dose of pyridoxine leads to a considerable reduction in the rate of oxidative metabolism of tryptophan and an increased rate of uptake into the brain and synthesis of serotonin, 46 suggesting that vitamin B 6 , alone or together with tryptophan, could have a useful antidepressant action.…”

Section: Vitamin B 6 In Depressionmentioning

confidence: 99%

“…46 As discussed above, pyridoxal phosphate acts to terminate the actions of steroid hormones, and tryptophan dioxygenase is induced by glucocorticoid hormones. In rats, a relatively high dose of pyridoxine leads to a considerable reduction in the rate of oxidative metabolism of tryptophan and an increased rate of uptake into the brain and synthesis of serotonin, 46 suggesting that vitamin B 6 , alone or together with tryptophan, could have a useful antidepressant action. Tryptophan is no longer generally available for therapeutic use, or as a supplement, because of the eosinophilia-myalgia syndrome associated with (at least one batch of) tryptophan, 47,48 and there have been no trials of pyridoxine that have shown any significant antidepressant effect except those involving depression associated with high-dose estrogens.…”

Section: Vitamin B 6 In Depressionmentioning

confidence: 99%

Vitamin B₆: Beyond Adequacy

Bender

2011

J Evid Based Complementary Altern Med

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There is good agreement concerning average requirements and reference intakes for vitamin B 6 but less agreement over safe upper levels from supplements. High-dose supplements cause sensory nerve damage. Supplements of vitamin B 6 have been advocated for treatment of the premenstrual syndrome, with little evidence of efficacy. There are plausible mechanisms for an antidepressant action and protection against steroid hormone-dependent cancers but no evidence from clinical trials. Pyridoxamine reduces the glycation of proteins and so could be beneficial in preventing the adverse effects of poor glycemic control in diabetes. There are plausible mechanisms for an antihypertensive action but only suggestive evidence from small intervention trials. There is no evidence that supplements of vitamin B 6 have any beneficial effect in hyperhomocysteinemia. There is neither a plausible mechanism nor any evidence from controlled trials for any effect of supplements of vitamin B 6 in preventing a decline in cognitive function with aging, amelioration of dementia or autism, or improvement of the carpal tunnel syndrome.Average adult requirements for vitamin B 6 are of the order of 1.3 to 1.4 mg/d, and reference intakes for adults are between 1.5 to 1.7 mg/d, with a slightly higher reference intake for people aged more than 65 years. These requirements and reference intakes have been based on normalization of tryptophan metabolism, optimization of plasma transaminase activity, and the plasma concentration of pyridoxal phosphate or total vitamin B 6 . 1-4 A number of dietary surveys have shown that a significant number of people in developed countries have inadequate intakes of vitamin B 6 , 5 and in various studies, 10% to 20% of healthy people show signs of biochemical inadequacy or marginal deficiency 6 by one or another of the indices of nutritional status.The main form of vitamin B 6 used in supplements is pyridoxine; as shown in Figure 1, this is readily phosphorylated and oxidized to the metabolically active coenzyme pyridoxal phosphate. Pyridoxal phosphate is involved in 3 main areas of metabolism: as the coenzyme for many reactions in amino acid metabolism, where it is the aldehyde group that is important 7 ; as the coenzyme for glycogen phosphorylase in liver and muscle, where it is the phosphate group that is important 8 ; and in attenuating the nuclear actions of steroid hormones, where it is again the aldehyde group that is important. 9 Pyridoxamine phosphate is formed in some reactions and is readily interconvertible with pyridoxal phosphate.In a small number of very rare genetic conditions, a mutation in a pyridoxal phosphate-dependent enzyme results in a very low affinity of the enzyme for its coenzyme, and the affected enzyme only has significant activity when the tissue concentration of pyridoxal phosphate is very much higher than normal. For these conditions, supplements of vitamin B 6 of between 200 and 1000 mg/d are required throughout life. [10][11][12] The antituberculosis drug isoniazid (iso-nicotinic acid ...

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High Doses of Vitamin B₆ in the Rat Are Associated with Inhibition of Hepatic Tryptophan Metabolism and Increased Uptake of Tryptophan into the Brain

Cited by 15 publications

References 21 publications

Tryptophan metabolism and vitamin B₆nutritional status in patients with schistosomiasis mansoni and in infected mice

Tryptophan metabolism and vitamin B₆nutritional status in patients with schistosomiasis mansoni and in infected mice

Non-nutritional uses of vitamin B₆

Vitamin B₆: Beyond Adequacy

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High Doses of Vitamin B6 in the Rat Are Associated with Inhibition of Hepatic Tryptophan Metabolism and Increased Uptake of Tryptophan into the Brain

Cited by 15 publications

References 21 publications

Tryptophan metabolism and vitamin B6nutritional status in patients with schistosomiasis mansoni and in infected mice

Tryptophan metabolism and vitamin B6nutritional status in patients with schistosomiasis mansoni and in infected mice

Non-nutritional uses of vitamin B6

Vitamin B6: Beyond Adequacy

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Product

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High Doses of Vitamin B₆ in the Rat Are Associated with Inhibition of Hepatic Tryptophan Metabolism and Increased Uptake of Tryptophan into the Brain

Tryptophan metabolism and vitamin B₆nutritional status in patients with schistosomiasis mansoni and in infected mice

Tryptophan metabolism and vitamin B₆nutritional status in patients with schistosomiasis mansoni and in infected mice

Non-nutritional uses of vitamin B₆

Vitamin B₆: Beyond Adequacy