The theophylline in tea may inhibit the synthesis of the active form of pyridoxal in the liver, lowering plasma levels.
Pyridoxal phosphate is the activated version of pyridoxal, part of the vitamin B6 group of vitamins (here). The vitamin functions in a large number of reactions as a cofactor for amino acid metabolism. Low plasma levels of pyridoxal phosphate are found in asthmatics and supplementation of asthmatics with pyridoxal phosphate causes significant and rapid improvements in the symptoms of asthma. In a study published in the American Journal of Clinical Nutrition in 19851, researchers measured the pyridoxal phosphate plasma levels of 15 patients with bronchial asthma and found them to be significantly lower than control subjects. When the researchers administered 50 mg pyridoxal phosphate to the subjects, their plasma and erythrocyte levels of pyridoxal phosphate did not improve in a sustained manner. However, the subjects did show rapid and significant decreases in the severity of wheezing and asthma attacks while taking the supplements.
Asthmatics taking supplemental vitamin B6 have been shown to require reductions in bronchodilator medication following administration of 200 mg per day of vitamin B6 as pyridoxine. However, this appears not to be due to raised plasma levels of pyridoxal phosphate. Because plasma levels of pyridoxal phosphate are considered the best indicator of vitamin B6 status it is unclear asthmatic subjects show improvements in symptoms without concomitant improvements in plasma levels of the vitamin. The low plasma levels of pyridoxal phosphate may relate to the use of theophylline as a bronchodilator. Some evidence shows that subjects taking theophylline have depressed plasma levels of pyridoxal phosphate. Further, supplementation of 200 mg of theophylline causes a significant reduction in plasma levels of the active pyridoxal phosphate but not of the inactive pyridoxal. Theophylline may inhibit the phosphorylation of pyridoxal and therefore reduce plasma levels of the vitamin2.
Because pyridoxal is phosphorylated in the liver, these results suggest that asthmatics have low levels of pyridoxal phosphate because theophylline interferes with phosphorylation of the vitamin in the liver. Long-term administration of theophylline may therefore detrimentally affect pyridoxal phosphate status. The ability of theophylline to depress pyridoxal phosphate plasma levels and induce poor vitamin B6 status also explains the ability of theophylline to induce seizures through inhibition of gamma aminobutyric acid levels in the central nervous system. The ability of vitamin B6 to alleviate such seizures is explained by the role of the vitamin as a cofactor in the synthesis of gamma aminobutyric acid. Theophylline metabolism in the liver may therefore interfere with the metabolism of vitamin B6 and this may have widespread effects on amino acid metabolism in the body as a whole, including the central nervous system. This illustrates the negative effect drugs can due to competition for metabolic pathways with nutrients.
