Breakfasting on half a grapefruit has long been seen as one of the healthiest ways to start the day, a virtuous alternative to tucking into cereal or a cooked breakfast. But could this supposed “superfood”, which is packed with vital vitamins and minerals, really be doing you more harm than good?
Researchers recently have warned that the fruit reacts with a large number of medicines taken by millions of Britons every day, causing devastating side-effects ranging from stomach bleeding to kidney problems, muscle aches and irregular heartbeats.
Doctors say the public are woefully ignorant about the dangers of mixing grapefruit with medicine and that many are putting themselves needlessly at risk.
So what is the truth behind the scare, and how can such a “healthy” fruit pose such a threat?
WHAT IS THE PROBLEM?
Astonishingly, just one glass of grapefruit juice is enough to treble the potency of some cancer, heart, cholesterol and painkilling drugs.
More than 20 years ago doctors discovered that grapefruit makes some prescriptions dangerously strong. But since then, the list of medicines affected by the fruit has soared.
Over the past four years, the number known to interact with grapefruit and cause serious side-effects has gone from 17 to 43, according to a report in the Canadian Medical Journal.
In the UK, almost all of those drugs are available on prescription (see table below). Another 42 medicines are thought to have milder, although still disturbing, side-effects.
Doctors are supposed to advise patients about the risks, while the warning also appears on patient leaflets that accompany drugs. But sometimes, amid the flurry of information that patients get when diagnosed a new drug, the warning is overlooked or quickly forgotten.
And the side-effects of grapefruit-related overdoses can be horrendous. Some patients suffer low blood pressure and immune system collapse.
HOW DOES THIS HAPPEN?
Scientists have only recently worked out how grapefruit makes drugs more potent.
The problem lies in chemicals in the fruit called furanocoumarins. These are produced by plants often as a defence mechanism against predators.
The concentrations in grapefruit are not toxic, but they interfere with a chemical naturally produced in our intestines called cytochrome P450 3A4.
This enzyme sits in the lining of the intestines and is involved in the metabolism of some drugs, controlling the amount that enters the bloodstream. Drug companies have to increase the dosage of some tablets to compensate for the action of the enzyme.
However, if furanocoumarins are present in the intestine, they stop cytochrome P450 3A4 from working. As a result, more of the drug gets into the bloodstream and a patient is at risk of an overdose.
A single helping of grapefruit can have an effect, even if consumed hours before the patient takes their medicine.
The effects of mixing medicine and grapefruit can be dramatic. In tests, patients taking the blood pressure drug felodipine had three times the level of the medicine in their blood after drinking grapefruit juice than those patients who’d had a glass of water.
People who eat lots of the fruit over a long period of time appear to be at even higher risk.
Researchers have shown that taking the cholesterol-lowering drug simvastatin with a 200ml glass of grapefruit juice every day for three days increased the drug’s concentration in the blood three-fold.
Dr David Bailey, a researcher at the Lawson Health Research Institute in London, Ontario, who published the study, said in summary: “One tablet with a glass of grapefruit juice can be like taking five or ten tablets with a glass of water. So you can unintentionally go from a therapeutic level [of the drug] to a toxic level just by consuming grapefruit juice.”
WHAT DRUGS ARE AFFECTED?
The range of drugs affected by grapefruit is vast and covers virtually every type of medicine from painkillers and sedatives to drugs that fight cancer and lower blood pressure.
One of the most common groups are the statins — simvastatin, lovastatin and atorvastatin — taken by some seven million Britons to lower cholesterol.
The antibiotic erythromycin is another common medicine made more potent when taken with grapefruit. It is used, among other things, to treat skin and urinary infections.
The drug is not particularly toxic, but an overdose can cause nasty symptoms including stomach upsets. And, crucially, too much erythromycin in the blood interferes with the way other drugs work.
The blood-thinning drug clopidogrel is also on the list. It is commonly prescribed after heart attacks, strokes or angina. Unusually it doesn't become more potent with grapefruit, but can stop working completely. The list of danger medicines also includes antipsychotic drugs — including treatments for anxiety, depression, bipolar disorder and schizophrenia — drugs for kidney, skin and blood cancers, blood thinning medication and painkillers.
The one thing that all the drugs have in common is that they are taken orally, usually as pills.
WHAT ARE THE EFFECTS OF MIXING GRAPEFRUIT AND MEDICINES?
The side-effects of mixing grapefruit with medicines vary hugely from drug to drug. But some can be deadly. Overdosing on cancer drugs, antibiotics and some antipsychotic drugs can cause irregular heart rhythms and even sudden death.
In the Nineties a patient in America died from an irregular heartbeat after taking the antihistamine allergy medicine Terfenadine twice a day while also drinking grapefruit juice two to three times a week. Doctors believed the two were connected.
High doses of anti-cancer drugs can suppress the activity of bone marrow, which creates blood cells and fights infection — putting people with weakened immune systems at further risk of illness.
Stomach bleeding can result from an overdose of blood-thinning drugs such as apixaban and rivaroxaban.
Overdosing on statins can lead to the painful and potentially dangerous breakdown of muscle tissue. As muscle proteins enter the blood, it can put the kidneys under extreme strain and may lead to kidney failure. Other symptoms include muscle pain and swelling, vomiting and diarrhoea.
Older people — who are less able to tolerate overdoses — are more likely to become seriously ill as a result.
CAN OTHER FRUITS HAVE THIS EFFECT?
Grapefruit is the biggest threat, but other fruits can interfere with drugs, too.
Seville oranges, used to make marmalade, and limes contain the same active ingredients that cause the drug problems.
One patient in Dr Bailey’s study suffered from kidney problems while taking the drug tacrolimus to suppress their immune system after an organ transplant.
He had eaten a staggering 1.5kg of marmalade during the preceding week — more than enough to make the drugs more potent.
Past research by Dr Bailey showed that orange and apple juices may reduce the effectiveness of drugs used to treat cancer, heart conditions and high blood pressure.
In tests, beta blockers, antibiotics and hay fever treatments were all weakened by juice drunk up to two hours previously.
The problem was caused by naringin (a chemical which makes citrus fruits bitter) which stopped the drugs moving from the small intestine into the bloodstream — the opposite of what happens with grapefruit.
WHAT SHOULD PATIENTS DO?
Dr Graham Archard, spokesman for the Royal College of General Practitioners, said: “It is vital that people do not ignore this. If they are on these medications, it is sensible not to eat grapefruit. While you may not have had problems in the past, that doesn’t mean you won’t get them in the future.
“The majority of these medications are prescription only and the doctor should inform patients if there are problems with grapefruit.
“But sometimes patients don’t take in all the information they are given, and sometimes doctors may forget, so it’s important to read the patient information leaflet.”
DRUGS THAT REACT WITH GRAPEFRUIT
ANTI-CANCER
Dasatinib (leukaemia)
Erlotinib (lung cancer and pancreatic cancer)
Everolimus (kidney cancer)
Lapatinib (breast cancer)
Nilotinib (leukaemia)
Pazopanib (kidney cancer)
Sunitinib (kidney/gastrointestinal cancer)
Vandetanib (thyroid cancer)
Venurafenib (skin cancer)
ANTI-INFECTIVE
Erythromycin (antibiotic)
Halofantrine (malaria)
Maraviroc (HIV)
Primaquine (malaria)
Quinine (malaria)
Rilpivirine (HIV)
ANTI-CHOLESTEROL
Atorvastatin
Lovastatin
Simvastatin
CARDIOVASCULAR
Amiodarone (heart rhythm disorders)
Apixaban (anti-clotting)
Dronedarone (heart rhythm disorders)
Eplerenone (heart failure)
Felodipine (high blood pressure/angina)
Nifedipine (high blood pressure/angina)
Quinidine (heart rhythm disorder)
Rivaroxaban (anti-blood clotting)
Ticagrelor (anti blood clotting after heart attack)
CENTRAL NERVOUS SYSTEM
Oral Alfentanil (Painkiller)
Oral fentanyl (painkiller)
Oral ketamine (painkiller, sedative)
Lurasidone (schizophrenia/mental health problems)
Oxycodone (painkiller)
Pimozide (schizophrenia/other mental health problems)
Ziprasidone (schizophrenia, mania, bipolar disorder)
GASTROINTESTINAL
Domperidone (anti nausea)
IMMUNO-SUPPRESSANTS
Cyclosporine (post organ transplant, rheumatoid arthritis, psoriasis)
Sirolimus (post organ transplant)
Tacrolimus (post organ transplant)
URINARY TRACT
Solifenacin (urinary frequency/incontinence)
Silodosin (enlarged prostate)
Tamsulosin (enlarged prostate)
— Daily Mail
