Green Tea May Weaken Nadolol's BP-Lowering Effect

Marlene Busko

January 13, 2014

FUKUSHIMA, JAPAN — A preliminary study reports that drinking green tea reduced the plasma concentration and the systolic-BP–lowering effect of the beta-blocker nadolol in 10 healthy young volunteers[1].

"We'd like to raise the possibility that green-tea consumption may change the plasma concentrations and pharmacological effect of nadolol," lead author Dr Shingen Misaka (Fukushima Medical University, Japan) commented in an email to heartwire . However, the "clinical study was just a small study in healthy adults," he cautioned. "Therefore, we consider that it's still insufficient to expand our findings to other beta-blockers, all green-tea products, and of course hypertension patients. . . . Further studies in a large population and different age groups will be needed."

The researchers showed that the blood-pressure–lowering effect of a single dose of nadolol was weaker after the volunteers had been drinking about 2 cups a day of green tea for 2 weeks than after they had been drinking this amount of water for 2 weeks.

Further, they showed that in cell-culture experiments, green tea appears to inhibit an organic anion-transporting polypeptide (OATP)—specifically OATP1A2—which is present in the intestinal epithelium and at least partly responsible for transporting nadolol into cells.

The study is published January 13, 2014 in Clinical Pharmacology & Therapeutics.

Green Tea–Nadolol Interaction

The catechins in green tea have been reported to prevent cancer or cardiovascular disease, but they might interfere with how certain drugs are absorbed by the body. Previous in vitro studies showed that catechins inhibit drug transporters such as P-glycoprotein (P-GP), OAP1A1, and OATP1A2, and nadolol is a substrate of OATP1A2.

These results suggested that drinking green tea might inhibit P-GP or OAT-mediated transport of nadolol into cells, which might alter the pharmacokinetics and pharmacodynamics of nadolol. The current study aimed to shed light on this potential interaction.

"Nadolol is prescribed for hypertension and angina pectoris and approved in many countries," Misaka noted. "However, nadolol is a relatively minor beta-blocker compared with other beta-blockers such as metoprolol and atenolol."

The researchers enrolled eight men and two women aged 20 to 30 years who had a body-mass index of 18.3 to 23.9 kg/m2, were nonsmokers, and were not taking any medications. Subjects were instructed to refrain from drinking green tea or apple, cranberry, grapefruit, or orange juice, since previous studies suggested that these juices inhibit OATP1A2 activity.

This was a randomized crossover study separated by a two-week washout period. For 14 days, the subjects were randomized to drink either 700 mL/day of green tea or water. Then they received a single oral dose of 30 mg of nadolol. Blood and urine was collected for testing, and blood-pressure and heart-rate measurements were done at specified times during two days of follow-up.

Greatly Reduced Plasma Nadolol Levels

When the subjects had drunk green tea as opposed to water during the 14 days prior to receiving the dose of nadolol, their plasma concentrations of nadolol were markedly reduced by 76%.

Green tea suppressed effect of nadolol on blood pressure, although there was great interindividual variability. At baseline, on average, the study subjects had a pulse rate of 67 beats/min, a systolic BP of 114 mm Hg, and a diastolic BP of 71 mm Hg. After a single dose of nadolol, the maximum decreases from baseline in these measures were 20%, 12%, and 11%, respectively, when the individuals drank water. These effects, especially the effect on systolic BP, were weakened after the subjects had been randomized to drinking green tea.

The in vitro experiments in this study showed that OAP1A2 was involved in transporting nadolol into cells, and green tea inhibited this action. "Inhibition of intestinal OATP1A2 may contribute to this interaction [between green tea and nadolol], although the involvement of other mechanisms such as upregulation of intestinal apical efflux transporters, eg, P-GP, cannot be excluded," Misaka explained.

"The clinical impact of the green tea–nadolol interaction may also depend on other factors including the dose of nadolol, the amount of green tea (catechins) consumed, and other coprescribed drugs," he observed.

Misaka had no conflicts of interest. Disclosures for the coauthors are listed in the paper.


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