In a small, controlled study of women with surgically removed ovaries, estradiol levels in the blood were significantly higher after estradiol was taken with grapefruit juice than when estradiol was taken alone.1 These results have been independently confirmed,2 suggesting that women taking oral estradiol should probably avoid grapefruit altogether.
Pomegranate juice has been shown to inhibit the same enzyme that is inhibited by grapefruit juice.3 , 4 The degree of inhibition is about the same for each of these juices. Therefore, it would be reasonable to expect that pomegranate juice might interact with estradiol in the same way that grapefruit juice does.
Studies have shown that grapefruit juice significantly increases estradiol levels in the blood.5 , 6 One of the flavonoids found in grapefruit juice is quercetin. In a test tube study, quercetin was found to change estrogen metabolism in human liver cells in a way that increases estradiol levels and reduces other forms of estrogen.7 This effect is likely to increase estrogen activity in the body. However, the levels of quercetin used to alter estrogen metabolism in the test tube were much higher than levels found in the body after supplementing with quercetin.
There is evidence from test tube studies that another flavonoid in grapefruit juice, naringenin, also has estrogenic activity.8 It has yet to be shown that dietary or supplemental levels of quercetin (or naringenin) could create a significant problem.
In controlled studies, the addition of 300 IU per day of vitamin D3 (cholecalciferol) did not improve the bone-preserving or fracture-preventing effects of hormone replacement with estradiol plus a progestin (a synthetic form of progesterone) in postmenopausal women without osteoporosis.9 , 10 However, in a controlled study of osteoporotic women, only those receiving both hormone replacement and vitamin D had increases in bone density of the hip; no improvement occurred in the hip with hormones alone.11 More research is needed to determine conclusively when vitamin D is important to add to hormone replacement.
1. Schubert W, Cullberg G, Edgar B, Hedner T. Inhibition of 17 beta-estradiol metabolism by grapefruit juice in ovariectomized women. Maturitas 1994;20:155–63.
2. Weber A, Jager R, Borner A, et al. Can grapefruit juice influence ethinylestradiol bioavailability? Contraception 1996;53:41–7.
3. Sorokin AV, Duncan B, Panetta R, Thompson PD. Rhabdomyolysis associated with pomegranate juice consumption. Am J Cardiol 2006;98:705–6.
4. Summers KM. Potential drug-food interactions with pomegranate juice. Ann Pharmacother 2006;40:1472–3.
5. Schubert W, Cullberg G, Edgar B, Hedner T. Inhibition of 17 beta-estradiol metabolism by grapefruit juice in ovariectomized women. Maturitas 1994;20:155–63.
6. Weber A, Jager R, Borner A, et al. Can grapefruit juice influence ethinylestradiol bioavailability? Contraception 1996;53:41–7.
7. Schubert W, Eriksson U, Edgar B, et al. Flavonoids in grapefruit juice inhibit the in vitro hepatic metabolism of 17 beta-estradiol. Eur J Drug Metab Pharmacokinet 1995;3:219–24.
8. Kuiper GG, Lemmen JG, Carlsson B, et al. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology 1998;139:4252–63.
9. Komulainen M, Kroger H, Tuppurainen MT, et al. Prevention of femoral and lumbar bone loss with hormone replacement therapy and vitamin D3 in early postmenopausal women: a population-based 5-year randomized trial. J Clin Endocrinol Metab 1999;84:546–52.
10. Komulainen MH, Kroger H, Tuppurainen MT, et al. HRT and Vit D in prevention of non-vertebral fractures in postmenopausal women; a 5 year randomized trial. Maturitas 1998;31:45–54.
11. Tuppurainen MT, Komulainen M, Kroger H, et al. Does vitamin D strengthen the increase in femoral neck BMD in osteoporotic women treated with estrogen? Osteoporos Int 1998;8:32–8.
Last Review: 05-01-2013
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