Dr. Ron’s Research Review – December 17, 2014

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This week’s research review focuses on vitamin B6 for Gestational Diabetes.

Estrogen Inhibits Tryptophan-Kynurenine-Xanthine Metabolism

Urinary excretion of metabolites of the tryptophan-nicotinic acid ribonucleotide pathway, urinary excretion of 4-pyridoxic acid and blood concentrations of estradiol and pyridoxal phosphate were studied in groups of post-menopausal women before or during treatment with natural estrogens, i.e. estradiol and oestriol, before and after loading doses of 9800 mumol L-tryptophan or 700 mumol L-kynurenine sulphate. Natural estrogens induced abnormalities of tryptophan metabolism similar to those induced by synthetic estrogens, and there was a dose related increase in urinary excretion of metabolites of the tryptophan-nicotinic acid ribonucleotide pathway before the kynureninase step. The increase in urinary excretion of these metabolites also after a loading dose of 700 mumol L-kynurenine indicates an inhibitory effect of estrogens on kynureninase in vivo. Evidence is presented that this inhibition is an effect mediated through decreased availability of vitamin B6, the coenzyme of kynureninase, although the possibility of a direct effect of estrogens on kynureninase cannot be excluded. (Wolf et al., 1980)

Vitamin B6 Restores Tryptophan Metabolism

Fourteen pregnant women were shown by the oral glucose tolerance test to have gestational diabetes. In 13 an increased urinary xanthurenic-acid excretion after an oral load of L-tryptophan indicated a relative pyridoxine deficiency. All patients were treated with vitamin B6 (pyridoxine) 100 mg/day for 14 days by mouth, after which the pyridoxine deficiency disappeared and the oral glucose tolerance improved considerably. Only two patients then had sufficiently impaired glucose tolerance to justify the diagnosis of gestational diabetes. (Bennink and Schreurs, 1975)

Dr. Ron


Articles

 

Improvement of oral glucose tolerance in gestational diabetes by pyridoxine
            (Bennink and Schreurs, 1975) Download
Fourteen pregnant women were shown by the oral glucose tolerance test to have gestational diabetes. In 13 an increased urinary xanthurenic-acid excretion after an oral load of L-tryptophan indicated a relative pyridoxine deficiency. All patients were treated with vitamin B6 (pyridoxine) 100 mg/day for 14 days by mouth, after which the pyridoxine deficiency disappeared and the oral glucose tolerance improved considerably. Only two patients then had sufficiently impaired glucose tolerance to justify the diagnosis of gestational diabetes; Our results substantiated our hypothesis that increased xanthurenic-acid synthesis during pregnancy may cause gestational diabetes. Treatment with vitamin B6 makes the production of xanthurenic-acid normal by restoring tryptophan metabolism and improves the oral glucose tolerance in patients with gestational diabetes.

Effect of natural oestrogens on tryptophan metabolism: evidence for interference of oestrogens with kynureninase.
            (Wolf et al., 1980) Download
Urinary excretion of metabolites of the tryptophan-nicotinic acid ribonucleotide pathway, urinary excretion of 4-pyridoxic acid and blood concentrations of oestradiol and pyridoxal phosphate were studied in groups of post-menopausal women before or during treatment with natural oestrogens, i.e. oestradiol and oestriol, before and after loading doses of 9800 mumol L-tryptophan or 700 mumol L-kynurenine sulphate. Natural oestrogens induced abnormalities of tryptophan metabolism similar to those induced by synthetic oestrogens, and there was a dose related increase in urinary excretion of metabolites of the tryptophan-nicotinic acid ribonucleotide pathway before the kynureninase step. The increase in urinary excretion of these metabolites also after a loading dose of 700 mumol L-kynurenine indicates an inhibitory effect of oestrogens on kynureninase in vivo. Evidence is presented that this inhibition is an effect mediated through decreased availability of vitamin B6, the coenzyme of kynureninase, although the possibility of a direct effect of oestrogens on kynureninase can not be excluded.


 

References

Bennink, H. J. and W. H. Schreurs (1975), ‘Improvement of oral glucose tolerance in gestational diabetes by pyridoxine’, Br Med J, 3 (5974), 13-15. PubMedID: 1131652
Wolf, H, et al. (1980), ‘Effect of natural oestrogens on tryptophan metabolism: evidence for interference of oestrogens with kynureninase.’, Scand J Clin Lab Invest, 40 (1), 15-22. PubMedID: 7367807