Anticipating possible interactions between drugs, foods and dietary supplements is a challenging area of integrative practice. When we think about interactions, we tend to envision risks associated with amplification of drug action or adverse effects. However, some interactions reduce drug efficacy, raising a different set of risks. For conditions such as hypertension, poor management resulting in diminished drug efficacy can elevate the risk of cardiovascular events.
Of all the types of interactions, pharmacokinetic interactions are the hardest to predict and detect. They are silent and subtle, reducing the absorption or enhancing the elimination of the drug, reducing overall exposure. They mimic partial compliance, where a patient skips doses, producing a partial relapse in symptomology, such as elevated blood pressure readings after a period of stable values.
It’s not uncommon for drugs to lose efficacy. This might occur gradually, over a period of weeks or months, where the therapeutic benefit weakens. This is often a result of adaptive metabolic or receptor-mediated adjustments that the body makes to cope with the unfamiliar chemical. Salient examples include caffeine and opioid tolerance. SSRIs and benzodiazepines can also lose some of their efficacy over time. In these cases, the effect is gradual, occurring over several weeks to months.
In contrast, interactions cause sudden changes in drug response within hours or days. If a previously stabilized patient with primary hypertension suddenly presents with elevated readings, you might investigate acute culprits (high sodium intake, stress, exercise the morning of the appointment, or the day before). But this also a time to ask the patient about any new supplements they just started taking, and check for possible interactions with their antihypertensive medication.
Vitamins and minerals generally do not cause pharmacokinetic interactions with antihypertensives. Some phytochemicals, on the other hand, can attach to enzymes and transporters involved in the absorption, metabolism, distribution, and elimination of some drugs. Common perpetrators of pharmacokinetic interactions are epigallocatechin gallate (EGCG, found in green tea), bergamottin and dihydrobergamottin (found in grapefruit), and berberine (an alkaloid that is sold as a dietary supplement).
The evidence on interactions between herbs, phytochemicals and antihypertensives is quite preliminary, and the long list of “interactions” retrieved in online databases and checkers is largely based on liberal and uncritical extrapolation of in vitro data. If we exclude the guessing and focus on direct clinical trial data, there are 3 interactions with potential clinical significance:
- Grapefruit and losartan. Grapefruit pulp and juice reduces blood levels of the active metabolite of losartan, potentially decreasing the antihypertensive effects of this drug [1]. It is unknown whether grapefruit seed presents similar risks, but caution is warranted based on high levels of one of the perpetrating constituents (dihydrobergamottin) in the seed.
- Berberine and losartan. Berberine can reduce the antihypertensive effects of losartan, an angiotensin receptor antagonist, by decreasing its conversion to its active form [2].
- Green tea and lisinopril. High dose standardized green tea reduces lisinopril absorption. In small pharmacokinetic study, green tea extract reduced peak plasma concentrations of lisinopril by approximately 71% and drug bioavailability (area under the curve (AUC) by 66% [3]. The interaction likely involves epigallocatechin gallate (EGCG)-mediated inhibition of organic anion transporters (OATPs) responsible for drug absorption.
Checking for interactions can be challenging and ineffective without a reliable resource. A good online checker should filter for clinical significance, exclude hypothetical “noise,” and undergo frequent updating as the evidence evolves.
Further reading
Drug-Nutrient Interactions: Solving Three Practical Problems
References
- Bailey DG, Dresser GK. Interactions between grapefruit juice and cardiovascular drugs. Am J Cardiovasc Drugs. 2004;4(5):281-97.
- Guo Y, Chen Y, Tan ZR, Klaassen CD, Zhou HH. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol. 2012 Feb;68(2):213-7.
- Misaka S, Ono Y, Uchida A, Ono T, Abe O, Ogata H, Sato H, Suzuki M, Onoue S, Shikama Y, Shimomura K. Impact of Green Tea Catechin Ingestion on the Pharmacokinetics of Lisinopril in Healthy Volunteers. Clin Transl Sci. 2021 Mar;14(2):476-480.
Integrative Pharmacology 