More grave statin side-effects

Lower intelligence, memory problems, nightmares, depression, suicide... Statins are the wonder drug for cutting cholesterol. But evidence of severe side-effects keeps piling up

Could statins, the cholesterol-lowering drugs taken by more than three million Britons, be doing more harm than good to many thousands of patients? This is the rather alarming suggestion to emerge from two new studies. The research challenges the medical convention that lowering your cholesterol is always a good thing - indeed, they suggest statins may affect intelligence, cause depression and even raise the risk of suicide. The studies add to a growing body of evidence that having low cholesterol levels may prove as dangerous as having high readings.

This has huge implications for British proposals to offer statins to all men over 50 and women over 60, even if they don't have a high cholesterol count. The NHS spends more than o500 million a year on statins. The drugs are commonly prescribed to cut the level of so-called 'bad' LDL cholesterol that our livers create. In patients vulnerable to heart attacks and strokes, the drugs reduce the risk of fatty deposits gathering in their bloodstream and causing life-threatening blood clots.

But cholesterol is also produced by the brain, where it is used to release vital chemicals called neurotransmitters that carry messages between brain cells. Now a study by Iowa State University suggests that statins inhibit this vital process. When brain cells are deprived of cholesterol, they are five times less effective at releasing chemical messengers, says the research, published in the highly respected journal Proceedings Of The National Academy Of Sciences.

'If you deprive cholesterol from the brain, then you directly affect how smart you are and how well you remember things,' says Yeon-Kyun Shin, the biophysics professor behind the study. 'This may lead to depression and irrational acts.' He believes this is directly caused by disruption in the neurotransmitter release in the brain. Indeed, statins were implicated in the suicide in April 2007 of London teacher Allan Woolley. After being prescribed the drug simvastatin, the housemaster at University College School in Hampstead complained of blackouts, insomnia and nightmares before he then killed himself by standing in front of a train. His family and friends said his death was completely out of character. The coroner ruled that the drug 'was involved' in his suicide.

Shin's findings reinforce another new study, which found that men with a combination of low cholesterol and depression are seven times more likely to die prematurely from suicide, accidents and other unnatural causes than men with only depression.

Scientists who followed nearly 4,500 Vietnam veterans over a 15-year period say the disturbing findings may be due to low blood cholesterol reducing levels of the brain's feel-good chemical messenger, serotonin. Low serotonin is linked to depression, anger, sleep loss and other problems, says Dr Joseph Boscarino, of the American Geisinger research institute, who did the research. 'While it's generally understood that having low cholesterol is a good health sign, combined with other factors, it could actually put a person at risk,' says the report. In fact, there is a significant body of evidence to show that low cholesterol may be as dangerous as high cholesterol.

These reputable studies show how people with markedly low levels of cholesterol are more likely to die from a variety of causes, including strokes, certain cancers, liver disease, lung disease and suicide. The deaths from these other causes mount so quickly that the mortality rate for those with low cholesterol equals the rate for people with very high cholesterol, who are likely to die from heart disease.

The findings do not question the standard medical advice that people with high blood cholesterol should diet or take statins. Current guidelines from the Department of Health say that the maximum healthy total cholesterol level should be less than 5.0 millimoles per litre of blood (mmol/l). But researchers worried about the harmful effects of low cholesterol estimate that the danger threshold may be just below 4.0mmol/l.

One report claims that women on low-cholesterol diets may face infertility problems. This small study of 300 patients by the Toronto Infertility Clinic says that cholesterol is essential for creating the sex hormones oestrogen and testosterone.

Other U.S. research found that women with low cholesterol could be twice as likely to suffer from depression or anxiety problems. Even more worrying, studies of older people have found that those on low- cholesterol diets have a much higher rate of stroke, possibly because cholesterol has a protective effect in mature brain linings.

But the link between low cholesterol, decreased serotonin and dangerous behaviour is particularly strong and disturbing. A study of 80,000 Swedes, for example, shows that men who murder in a fit of rage tend to have below-average cholesterol. Irish doctors report that cholesterol levels are significantly lower in people who have been admitted to hospital after harming themselves. Research in the animal kingdom supports the existence of this problem: studies of captive monkeys reveal that they become abnormally aggressive when put on low-fat diets. And studies on mice indicate that cholesterol may help the brain to suppress reckless impulses.

Meanwhile, the NHS continues to prescribe ever more statins. There is no doubt that statins are life- saving drugs for people who have already had a heart attack. But the guidelines are constantly being revised. Until 2006, statins were prescribed only to men and women under 75 who had a 20 per cent risk of developing coronary heart disease within ten years. Now, the NHS recommends they are given to any adult with a total cholesterol of more than 5.0mmol/l who is thought at risk.

Moving forward, the Government argues that giving all men over 50 and women over 60 a daily dose of statins would save lives, NHS funds and doctors' time. However, Dr Alastair Dobbin, a GP based in Edinburgh, is highly critical of the policy. He has written in the British Medical Journal severely criticising the 'statins for all' approach. He believes it's an expensive waste of time that leaves millions of people falsely reassured and which may have damaging side-effects. 'The new Iowa study shows that we should be really cautious about handing out statins the way we do,' he says. 'We should be very careful about giving a drug to healthy people where there is any risk of any side-effects.'

He adds: 'Research shows that in people over 69 who've had no symptoms of diabetes, angina, stroke or heart attack, statins don't reduce mortality. 'They're invaluable for patients who have had these symptoms, but there's no scientific case for giving them to anyone else. 'It's a sheer waste of money, but the Government is ignoring the research.

'On the other hand, studies have found that patients have suffered memory loss with statins - some people have been unable to even recognise their spouse - yet the problem has disappeared after they stopped taking the drug.' Yet rather than investigating the disturbing links with statins further, the medical establishment has largely hushed, ignored or discredited them, for fear of confusing the 'high cholesterol is bad' message.

One campaign group, The International Network of Cholesterol Skeptics, includes on its website a list of academic research articles and letters it feels have been unfairly rejected by medical journals. For the sake of everyone's health, and to save the NHS millions it hasn't got, perhaps the answer is to rewrite the public health message to read: moderation in all things - including cholesterol control.

GREAT MEDICAL U-TURNS

The idea that low cholesterol could be bad for you isn't the only health message that's been revised. Here are some others:

EGGS: Only last month, research backed by the British Nutrition Foundation put cholesterol-rich eggs firmly back on our healthy menus. For years, eggs had been associated with an increased risk of heart disease; this has been shown to be wrong.

BACKS: Conventional wisdom held that a bad back should be treated with bed rest. But experts changed their minds, and now stress the importance of movement and exercise.

TONSILS: A tonsillectomy was once almost a childhood rite of passage but are now so discredited that children who do need their tonsils removed can't get the operation.

NUTS: For ten years, pregnant and breastfeeding women were advised not to eat peanuts if there was a family history of allergies. But last December, the Food Safety Agency said it was no longer backing the policy because 'current evidence' does not support it.

MAGGOTS AND LEECHES: These were banned from mainstream therapy after the NHS was formed in 1948. But, in recent years, maggots have been used to keep wounds clean, and leeches to help healing after surgery.

NYMPHOMANIA: This was regarded as a mental illness until the Sixties. These days, women who don't have a strong sex drive are thought to be 'unwell', suffering from Female Sexual Dysfunction.

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CABBAGE VERSUS CANCER

A vegetable-based drug could inhibit melanoma, US scientists believe. Compounds extracted from green vegetables such as broccoli and cabbage could be made into a potent drug against melanoma. Tests on mice suggest that these compounds, when combined with selenium (found in cereals, meat and fish) target tumours more safely and effectively than conventional therapy.

"There are currently no drugs to target the proteins that trigger melanoma," says Gavin Robertson, Associate Professor at Penn State College of Medicine. "We have developed drugs from naturally occurring compounds that can inhibit the growth of tumour in mice by 50 to 60 per cent with a very low dose."

The search for a drug to block the protein led them to a class of compounds called isothiocyanates, which are naturally occurring in cruciferous vegetables, though in very low doses.

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