Labeled content of two furanocoumarins in dietary supplements correlates with neither actual content nor CYP3A inhibitory activity

Karen M Vandermolen,Garrett R Ainslie,Mary F Paine,Nicholas H Oberlies

doi:10.1016/j.jpba.2014.05.038

Abstract

Dietary supplements are a multi-billion dollar business, with yearly profit increases. Allegedly safe, these supplements are marketed to a variety of niches, encompassing claims from immune support to weight loss. Six sports nutrition supplements were acquired that were labeled to contain the furanocoumarin(s) bergamottin and/or 6′,7′-dihydroxybergamottin (DHB), both of which are potent irreversible inhibitors of the prominent drug metabolizing enzyme cytochrome P450 3A (CYP3A). Both furanocoumarins are typically present in grapefruit juice, which has been shown to inhibit intestinal CYP3A, perpetrating an increase in the systemic exposure of certain concomitant ‘victim’ drugs. The acquired supplements were analyzed using ultra-performance liquid chromatography coupled to both a photodiode array (PDA) detector and a triple quadrupole mass spectrometer (MS). Contrary to the product labeling, four of the supplements contained no detectable quantities of either furanocoumarin (LOD 0.060μg/capsule), while two of the supplements contained minimal amounts (one contained 12.13 (±0.23) μg bergamottin and 65.51 (±0.64) μg DHB per capsule; the other contained 2.705 (±0.069) μg bergamottin per capsule and no detectable quantities of DHB). A CYP3A inhibition bioassay was used to assess whether the actual content of the furanocoumarins correlated with CYP3A inhibitory activity. Despite the low amounts of bergamottin and DHB, CYP3A inhibition by the supplements was greater than could be accounted for by the two furanocoumarins. The additional activity suggests the presence of other potent or highly abundant CYP3A inhibitors.

Highlights

Dietary supplements are a thriving industry in the United States, surpassing $30 billion in sales in 2011 [1] and encompassing various facets of the market
Sports nutrition supplements represented 12% of the total sales [1], [3]. Some of these supplements are labeled to contain bergamottin and/or 6′,7′-dihydroxybergamottin (DHB) (Fig. 1), two furanocoumarins found in grapefruit juice that have been shown to interfere with cytochrome P450 3A (CYP3A) in the intestine through irreversible inhibition of the enzyme [4], [5], [6], [7]
All of the supplements analyzed were labeled to contain bergamottin and/or DHB, but only one contained detectable quantities of these analytes, and, even in much lower amounts than the label claimed. While these results reflected poorly on label accuracy, the low quantities were initially reassuring in consideration of possible supplement–drug interactions, when one product was labeled to contain 300 mg DHB per capsule

Summary

Introduction

Dietary supplements are a thriving industry in the United States, surpassing $30 billion in sales in 2011 [1] and encompassing various facets of the market They can include single- or multivitamins, minerals, herbs and botanicals [2], weight-loss aids, and sports nutrition products. Sports nutrition supplements represented 12% of the total sales [1], [3] Some of these supplements are labeled to contain bergamottin and/or 6′,7′-dihydroxybergamottin (DHB) (Fig. 1), two furanocoumarins found in grapefruit juice that have been shown to interfere with cytochrome P450 3A (CYP3A) in the intestine through irreversible inhibition of the enzyme [4], [5], [6], [7]. Supplements containing bergamottin or DHB at similar amounts may pose a risk for consumers taking concomitant medications that undergo extensive CYP3A-mediated intestinal metabolism [6], [7], [8], [9]

Methods

Results

Conclusion