Grapefruit, CYP3A4 and deep vein thrombosis

Here's an interesting story off the news:

Grapefruit diet almost cost woman her leg

PARIS, April 3, 2009 (AFP) - A woman who ate a grapefruit each day almost had to have her leg amputated because of a dangerous blood clot, according to an unusual case study reported in the Lancet.

Emergency doctors in Olympia, in the US Pacific coast state of Washington, treated the 42-year-old woman in November 2008 after she was admitted with shortness of breath, dizziness and difficulty walking. An ultrasound scan found she had a large clot blocking the veins of her left leg.

She was in imminent danger of losing the limb to gangrene, but doctors administered a clot-busting drug directly into the blockage and safely dissolved it.

The physicians found she had taken a relatively long car journey, of about an hour and a half, the day before; took a daily dose of oestrogen oral contraceptives; and had a genetic variant, called the factor V Leiden mutation, which is linked to a blood-clot disorder.

All are well-established factors for causing deep vein thrombosis (DVT), as these dangerous events are called.

But what "may well have tipped the balance" is that she had been eating a grapefruit every morning under a weight-loss diet begun three days earlier, the report said.

Grapefruit juice is known to block the action of an enzyme called CYP3A4 which breaks down the contraceptive hormone oestrogen.

This in turn boosts levels of coagulability - the tendency of blood to clot.

Grapefruit juice is broken down only very slowly, which means that it has a cumulative effect if taken daily. Thus, on the third day of her diet, the patient's oestrogen levels would have been many times above normal, helping the clot to form.

DVT has been popularly termed "economy-class syndrome," as it is associated with passengers hunched up on cramped seats in long-haul flights.

But experts say DVT can be inflicted by any kind of immobility - in cars, the office or at home - that causes the leg to be bent for long periods and prevents blood from flowing. The clotting risk is amplified by oral contraceptives and heritability.