They have prevented countless heart attacks and strokes and probably saved the lives of millions in the process.

And despite being heralded as game-changers when they were first rolled out to the masses in the 1980s, statins have got a bad rap in recent years.

On their way to becoming one of the most prescribed drugs in the world, a host of research began linking them to a wide range of debilitating side effects — from memory loss to muscle pain, migraines and even diabetes.

It is estimated that as many as half of users stop taking them entirely or don’t use them properly because of the supposed risks, which severely limits their cholesterol-lowering powers.

But a growing number of studies have started pushing back against claims statins are the true culprit behind all of the side effects, which many experts suspect are just as prevalent among people not on the drugs.

Yesterday, a landmark Oxford University study revealed muscle pains are no more common in people on statins, despite being listed as an official symptom by the NHS and health chiefs around the world.

That research, on more than 150,000 people, concluded that the symptoms are in fact caused by the natural effects of ageing. 

A similar theory might also explain why the drugs — taken by 8million Britons and 32million Americans — are constantly linked to memory and sight problems. 

Professor Sir Nilesh, medical director at the British Heart Foundation, told MailOnline: ‘Statins are an important and proven treatment for preventing coronary heart disease.

‘But their use has been clouded by the perception that they cause significant side effects, like muscle aches but also memory loss, sleep disturbance and erectile dysfunction. 

‘However, these complaints are not uncommon in the general population for a whole variety of reasons. Therefore when patients take a statin and develop such symptoms, they understandably attribute them to the statin when it may not be the cause.’

Statins are a group of pills that stop the liver producing ‘bad’ cholesterol, known as low-density lipoprotein (LDL) cholesterol. Over time, its build-up can lead to hardened and narrowed arteries and heart disease — one of the world’s leading causes of death.

People are currently prescribed statins if they have been diagnosed with the disease, or have a family history of it. The tablets, which cost just 20p a pill and are proven to be life-savers, are taken once a day.

Here, MailOnline breaks down the biggest myths around statins and their potential side effects: 

Millions are able to live normal lives thanks to the cholesterol-busting effects of statins but the drugs have been linked to numerous side-effects that put some off the medication. However, many of these supposed symptoms — including memory loss, diabetes and headaches — may actually be a result of other lifestyle factors, experts have found

Statins are the most widely prescribed drugs in the world, with around 8million Britons and 32million Americans taking them every day to cut their risk of heart complications due to high blood pressure

Muscle pain

The NHS lists muscle pain as one of the ‘common side effects’ of statins and also suggests weakness can be caused by the drugs.

But a review by Oxford University published in The Lancet on Monday suggests the aches and pains may actually be just the natural signs of old age. 

Researchers looked at rates of the side effects in 155,000 patients who took statins or placebos in 23 randomised trials. 

The history of statins

1976

Japanese biochemist Akira Endo isolates mevastatin — the first statin drug — from a fungus.

Animal trials showed the drug lowered cholesterol in dogs, rabbits and monkeys.

However, the drug was never marketed after rat trials showed it could be toxic.

1978

Alfred Alberts discovered lovastatin while working at Merck Research Laboratories.

It was also discovered independently by Dr Endo for the Sankyo company within a year. 

Merck began clinical trials in 1980, but were paused after Sankyo tests of the chemically similar mevastatin found it was toxic in animals.

But trials on lovastatin found no similar issues and in 1983 clinical development was restarted by Merck. 

1987 

Lovastatin becomes the first statin to be approved by the US Food and Drug Administration (FDA).

It reached sales of more than $1billion (£858million) in its first year.

1997 

Atorvastatin is approved. It is sold by Pfizer as Lipitor and is the most popular statin in use today.

It followed the approvals of pravastatin in 1991 and fluvastatin in 1994.

2012

FDA introduces safety warnings on statins stating a small increased risk of higher blood sugar levels and type 2 diabetes diagnosis. 

In total 27.1 per cent of patients on the drugs reported muscle pain or weakness, compared to 26.6 per cent of those who were given the placebo.

After the first year of treatment, there was no difference between those given statins and those given dummy tablets.

The researchers found stronger doses carried a slightly higher risk of muscle issues, but most cases are mild.

They said the results will help patients and doctors ‘make informed decisions’ when considering if they should stop taking their pills — and should continue taking them unless the drugs are proved to cause the pain.

Lead researcher Professor Colin Baigent, an epidemiologist at Oxford, said if a patient on statins suffers muscle pain, it is ‘most likely due to other causes’.

Cataracts

Statins have also been linked with an increased risk of developing cataracts.

Cataracts are when the lens, a small transparent disc inside the eye, develops cloudy patches. Over time these patches usually become bigger causing blurry, misty vision and eventually blindness.

Around 330,000 surgeries for the condition are performed every year in England alone, making it the most common operation in the country. They affect around 24.4million adults aged over 40 in the US.

A series of studies over the past two decades have suggested statins may significantly raise the risk of cataracts.  

But research by cardiologists at Peking University First Hospital in Beijing, China, concluded ‘there is no clear evidence showing that statin use increases the risk of cataracts’ in humans after a major review in 2016.

The review, published in the Journal of the American Heart Association, looked at 17 studies in the US, UK, Canada, Australia, Europe and Asia, with a total of more than 313,000 patients included.

Six of the papers compared cases in people given statins or placebos and all 17 investigated the risk of cataracts with statin use. Patients were aged from 30 to 85.

Overall, there was a 13 per cent increased risk of developing cataracts in six of the long-term studies that followed statins patients for at least five years.

Interestingly, the risk was actually 11 per cent lower in more rigorously controlled studies.

Writing in the journal, the authors said: ‘Based on the present meta‐analysis of these studies, we could only conclude that there is no clear evidence showing that statin use increases the risk of cataracts. 

‘The most likely case is that there is no association between statin use and cataracts. Because of the considerable benefits of statins in cardiovascular patients, this issue should not deter their use.’

Sir Nilesh told MailOnline: ‘The most likely case is that there is no association between statin use and cataracts. Because of the considerable benefits of statins in cardiovascular patients, this issue should not deter their use.’

Memory loss

The NHS lists memory problems as an ‘uncommon’ side effect of statins, while the US Food and Drug Administration (FDA) warns ‘some people have developed memory loss or confusion’ on the drugs’ labels.

WHAT ARE STATINS? 

Statins are a group of medicines that can help lower levels of ‘bad cholesterol’ in the blood.

Having too much of this type of cholesterol — called low-density lipoprotein (LDL) cholesterol — can lead to the thickening of the arteries and cardiovascular disease.

Statins work by stopping the liver from producing as much LDL.

Previous studies have found that the drug will prevent one heart attack or stroke for every 50 people taking it over five years.

The drug comes as a tablet that is taken once a day.

Most people have to take them for life, as stopping will cause their cholesterol to return to a high level within weeks.

Some people experience side effects from the medication, including diarrhoea, a headache or nausea.

People are usually told to make lifestyle changes in a bid to lower their cholesterol — such as improving diet and exercise habits, limiting alcohol consumption and stopping smoking — before being prescribed statins.

The medicines watchdog issued the warnings because some people on the drugs reported suffering with problems after starting the medication.

But researchers have found no evidence the drugs actually cause the issue, with studies in fact showing they can help reduce the chance of developing dementia in the long-term. 

High cholesterol is one of the main risk factors for the memory-robbing condition.

Experts at John Hopkins University in Baltimore, Maryland, reviewed 16 studies of more than 23,000 patients that measured people who were and weren’t taking the drug’s memory, attention and problem-solving.

The review, published in Mayo Clinic Proceedings in 2013, only included patients with no history of cognitive decline.

Three studies found there was no association between using statins and dementia, while five found the drugs actually improved the chances of staving off the condition.

Overall, people given statins had a 29 per cent lower incidence of dementia. 

Study author Dr Kristopher Swiger, a cardiologist at JHU, said: ‘All medications, including statins, may cause side effects, and many patients take multiple medicines that could theoretically interact with each other and cause cognitive problems. 

‘However, our systematic review and meta-analysis of existing data found no connection between short-term statin use and memory loss or other types of cognitive dysfunction. 

‘In fact, longer-term statin use was associated with protection from dementia.’ 

Researchers said it ‘makes sense that statins could be protective in the brain against dementia’ because reducing bad cholesterol improves blood flow to the brain.

This helps prevent vascular dementia particular, which is usually caused by blockages in small blood vessels in the brain.

Headaches

Statins have been widely linked to headaches since they first exploded on the scene.

But Sir Nilesh said the symptom may not actually be being caused by the drugs themselves.

Much like with muscle pains, headaches are an everyday occurrence that become more prevalent in old age, when people are more likely to start taking statins.

He told MailOnline: ‘Headaches are not uncommon symptom in the general population for a whole variety of reasons.

‘Therefore, when patients take a statin and develop such symptoms, they understandably attribute them to the statin when it may not be the cause.’

In fact, some researchers suggests the drugs should actually be prescribed to people who suffer a certain type of migraine.

Although it may sound counter-intuitive, they believe people who suffer migraines with aura could benefit more from taking the drugs because of their greater risk of heart attacks and stroke.

Around one in five women and one in 15 men suffer migraines, with a severe headache preceded by an ‘aura’ affecting vision balance and coordination in about 30 per cent of cases.

Writing in the British Journal of GPs in 2015, Dr David Kernick, a GP at the Exeter Headache Clinic, argued statins should be prescribed to people who suffer the condition earlier than the rest of the population.

But other experts say more evidence is needed before any rule change.

Professor Peter Weissberg, consultant cardiologist at the Addenbrooke’s Hospital in Cambridge and medical director at the BHF, said: ‘We would need more evidence, from randomised clinical trials or case controlled studies, that prescribing statins for people with migraine would indeed bring about a reduction in heart attacks and strokes before changing guidelines.

‘This may be because the processes underlying heart attacks and strokes are different in migraine sufferers from the rest of the population, in which statins have been shown to be beneficial.’

Diabetes

Health chiefs introduced safety warnings on statins bottles in 2012 due to concerns they may cause a small increased risk of higher blood sugar levels.

This can lead to type 2 diabetes, in theory.

However, the reality is not quite as clear-cut as that.

A paper by experts at the Albert Einstein College of Medicine in New York in 2017 found pre-diabetics are 36 per cent more likely to be diagnosed with the condition after taking statins.

But critics insisted the results, published in the British Medical Journal, did not conclusively show the cheap pills increase the risk of developing the full-blown condition in people with normal blood sugar levels.

Medics also insist the benefits of statins still outweigh the slim odds of developing diabetes – even for patients on the brink of being diagnosed.

Sir Nilesh told MailOnline: ‘The risk of developing diabetes is small.

‘And for the vast majority of patients in whom statins are recommended, the benefits far outweigh the risks.

‘Existing guidelines on who should be recommended a statin reflect the risks of possible side effects with the cardiovascular benefit to patients.’

Grapefruit 

Finally, many statin users are warned not to eat grapefruit because of the fruit’s effect on how the body processes the drug.

Grapefruit contains chemicals called furanocoumarins, which block an enzyme in the intestine that normally breaks down statins and some other drugs.

This means the statins build up in the bloodstream rather than being processed properly, which can increase the risk of other side effects.

But grapefruit only appears to have a large effect on certain statin medications, with others seeing little to no problems.

Atorvastatin, sold as Lipitor, lovastatin, sold as Mevacor, and simvastatin, sold as Zocor, are the only drugs known to be particularly affected by the chemicals, according to Dr Jorge Plutzky, an associate professor of medicine at Harvard Medical School.

In contrast, there appears to be no interaction in people taking fluvastatin (Lescol), pitavastatin (Livalo) pravastatin (Pravachol) and rosuvastatin (Crestor).

Sir Nilesh said: ‘If you take simvastatin, you shouldn’t drink grapefruit juice as it increases the concentration of the drug in the blood stream, increasing the risk of side effects. 

‘If you take another type of statin, limit your intake of grapefruit juice to very small quantities or you may want to avoid it altogether.’ 

Johnny Depp told a court of the moment his marriage to actress Amber Heard fell apart – because he took his own boots off when he got home.

Amber, he said, had a routine that she would get him a glass of wine and remove his footwear as soon as he got home. 

But one day she was on the phone, so he took his own boots off rather than wait.  

‘I worked quite a lot and when I came home from work I’d come in the house and she’d sit me down and give me a glass of wine and take my boots off and set them to the side,’ he told the court in Fairfax, Virginia.

‘I’ve never experienced anything like that in my life. I never experienced that and it became a regular thing, kind of routine.

Depp got emotional as he talked about how good his relationship with Amber Heard was at the beginning but how it fell apart after he took his own boots off

‘No, no, no that’s my job. You don’t do that, I do that,’ Amber allegedly told Johnny after he had removed his own footwear

Depp said under oath that his wife ‘became another person, almost’ within 18 months of the boots incident

‘One night I came home and she was on the phone, I took my boots off, suddenly Miss Heard approached with this look on her face, she just said what did you just do? What did you do?’

He asked her what she meant and she replied: ‘You took your boots off.’

‘Yes I did, he said he told her. You were busy.’

But Amber told him: ‘No, no, no that’s my job. You don’t do that, I do that. 

‘Then she said “Let me get you a glass of wine.” I did take pause of course, the fact she was visibly shaken or upset that I had broken her rules of routine.

‘Once you notice something like that you start to notice other tidbits that come out.

‘Then within a year a year and a half she had become another person, almost.’

Depp, 58, was testifying in the trial in which he is suing Heard for libel over a 2018 op-ed that she wrote for the Washington Post in which she wrote about her alleged domestic abuse.

Heard, 35, is countersuing for $100 million, claiming that he smeared her when he accused her of lying.

He said in the beginning his relationship with Heard, who he met on the set of the 2011 movie The Rum Diary, was ‘too good to be true’.

‘She was attentive, she was loving, she was smart, she was funny, she was understanding. We had many things in common, certainly blues music, literature. 

‘For that year, or year and a half it was amazing.’

‘From the beginning of our relationship for a good year and a half she was wonderful and then things just started to change or things started to reveal themselves is a better way to put it.’

He said he called her Slim and she called him Steve after the Lauren Bacall and Humphrey Bogart characters in the movie To Have and Have Not.

He explained that he was the craggy Bogart and she was ‘this beautiful creature, this stunning creature,’ the much-younger Bacall.

He said it was during a kissing scene in The Rum Diary that he realized he had feelings for Heard, saying he ‘felt something he shouldn’t be feeling.’

She later went to his trailer and they kissed again. 

Judge Penney Azcarate who is presiding over the sensational trial in Fairfax, Virginia 

The Pirates of the Caribbean actor told the court Tuesday that he started popping pills when he was just 11 and by the time he was 15 he had ‘done all the drugs that I am aware of,’ Tuesday. 

He started on tablets his mother took for her nerves and progressed from there, he told the court.   

‘I’d bring my mum her nerve pill, I’d take one myself to escape caring so much, feeling so much – to escape the chaotic nature of what we were living through. 

‘Can’t say I’m proud of admitting that’.

He said after taking his mother’s pills he moved on to marijuana and other drugs.

He said: ‘I’ve never taken any substance for a party. I’ve taken these substances on and off to numb myself of the ghosts, the wraiths that were still with me from my youth. 

‘Essentially self medication, one of those get-me-out-of-here moments. You want to escape from your own brain, your own head’.

Depp said that by 15 he had ‘done all the drugs I was aware of’ but he didn’t continue at such a rate.

He said there were ‘many years’ he didn’t even have a drink’ and that he ‘wasn’t dropping acid every five minutes’.

And he said that his ex-wife’s claims about his drug abuse were exaggerated.

He said: ‘The characterization of my ‘substance abuse’ that’s been delivered by Miss Heard is grossly embellished and I’m sorry to say but a lot of it is just plainly false

‘It was an easy target for her to hit because once you’ve trusted somebody for a certain amount of years and you’ve told them all the secrets of your life that information can be used against you, especially if it’s taken to a point that’s teetering on impossible, teetered over impossible at times.

Depp and Heard called each other Steve and Slim after the Humphrey Bogart and Lauren Bacall  characters in the movie To Have and Have Not

Johnny Depp said ex-wfe Amber Heard always insisted she take his boots off and pour him a glass of wine when he got home

Heard and Depp in the movie The Rum Diary where they met. Johnny said he ‘felt something he should not have felt’ during a kissing scene in the movie

‘I am not some maniac who needs to be high or loaded all the time. 

‘In fact before Australia I’d been off of alcohol for about 18 months,’ he added referring to the time when he lost part of a finger, when, he claimed, Heard threw a bottle at him.

But he admitted that he got hooked on the painkiller Roxycontin – which he called Roxies – after getting sciatica from throwing a chair through a window in Pirates of the Caribbean 4.

 ‘It’s not like you take those pills to get high, you’re taking those pills to get well or better because if you’re without the pill your body will start to go into withdrawal,’ he said.

Depp shook his head and smiled when asked if he had done opiates since detoxing, telling the jury: ‘No I can’t.

‘Once you’ve been bit you’ll be bit again.’  

Depp apologized for sending his best friend vile texts about Heard saying he wanted to see her ‘rotting corpse decomposing in the f***ing trunk of a Honda Civic’.

‘I’m ashamed of some of the references made. I’m embarrassed that at the time the heat of the moment, the heat of the pain that I was feeling went to dark places.  

He said: ‘Sometimes pain has to be dealt with with humor and sometimes dark, very dark humor.

‘I grew up watching Monty Python so it can tend to get into dark humor. It can tend to get into…words are used for emphasis and words are used to express what you’re feeling at the time. It’s just like growing up, you learn from those mistakes, you learn from those things and you move forward’.

Earlier, Depp had talked about his upbringing, saying he had been regularly abused by his mother Betty Sue Palmer, who died in 2016.

But he said he learned a lot from his parents, especially about bringing up children. 

‘I knew exactly how to raise children when my girl Vanessa (Paradis) got pregnant I knew exactly how to raise children which was to do the opposite of what they did.

Depp said he learned how to bring up children from his mother Betty Sue Palmer. ‘Justdo the opposite of what she would do’

Depp and Heard met on the set of the 2011 movie The Rum Diary, turning up on the red carpet together for its London premiere

Depp with parents Betty Sue Palmer and John Christopher Depp and then-girlfriend Vanessa Paradis when he received a star on the Hollywood Walk of Fame in 1999

Never raise your voice in front of the children, never. Screaming out the word no to them. I never wanted to tell my kids no. 

‘I wanted to show them there are options – you don’t have to stick the coat hanger in the electrical socket.

‘Talk to them, if you understand the repercussions of something you won’t go there…give this some thought. That could kill you so I’d ease them away from things of that nature with more of a conversation as opposed to a flat out don’t you ever do that again, and threats. 

‘I did not raise my children that way.’ 

He told of ‘verbal abuse, name calling and bullying’ by his mother, who he described as ‘very unpredictable.’.

She took any ‘opportunity to be as cruel as anyone could be,’ he said. 

Depp laughed nervously as he recalled an ashtray being flung at him that hit him in the head, being beaten with high heel shoes, telephones, ‘whatever’s handy.’

‘In our house we were never exposed to any type of safety or security, the only thing to do was stay out of the line of fire,’ he said, adding, ‘When she was going to get riled up and somebody was going to get it and generally it was me.’ 

‘Physical violence, physical abuse. That was a constant. We were all somewhat shell-shocked. She’d walked past, you’d shield yourself because you didn’t know what would happen,’ Depp said. 

He talked about how his mother gave him and his two siblings cruel names.

Johnny Depp gestures while giving testimony during the trial. He said he started popping his mother’s nerve pills when he was 11 and by the time he was 15 had tried every drug he knows of

Amber Heard and her attorney Elaine Bredehoft during the trial on Tuesday. Heard is countersuing Depp for $100 million claiming he libeled her when he said she lied in a Washington Post op-ed

‘My brother wore glasses so he was Four Eyes. His teeth were messed up in the front so he was Buck Tooth.’

He said his mother called his sister Violet although her real name is Christie.

‘My mother despised my father’s parents. Grandmother’s name was Violet.

‘So my mother said, come here Violet, get in here Violet. Christie, my sister, knew very well that was a deep cut psychologically, emotionally, but you had to take it. 

‘You just had to take the pain.’

He said he had a lazy eye, and at one stage had to wear a patch over his good eye to try to strengthen the other.

”She would call me Cock eye or One Eye, anything she could get to demean, humiliate. 

‘The psychological abuse was almost worse than the beatings,’ Depp added. ‘They were just physical pain, and the physical pain, you learned to deal with it, accept it. 

‘But the psychological and emotional abuse that’s what kind of tore us up.’

 He said his father, John Christopher Depp was a kind stoic man who never lost his temper or attacked Betty Sue, until one day when Johnny was 15 he walked out and didn’t return.  

Attorneys for Heard have argued she told the truth and that her opinion was protected as free speech under the U.S. Constitution’s First Amendment

Depp arrives at the courthouse in Fairfax, Virginia, to give evidence in the trial

‘When my father left I didn’t realize,’ Depp said. ‘He left for work one morning, was packing his car and he left. 

‘Hours later my mom came home from work, about 3.30 in the afternoon. She walked in the door and stopped and walked around, she felt something. She said your daddy’s gone. He’s gone, he’s gone. 

‘She ran into their bedroom and into their closet, she opened the door and there was his rack of clothing and all his belongings were gone. She was quite upset. I took her car and drove to my father’s work and sat down in front of him at 15. 

I’d bring my mum her nerve pill, I’d take one myself to escape caring so much, feeling so much – to escape the chaotic nature of what we were living through 

‘I said, Listen, seems somebody stole all of your clothes and he said yeah, I’m done. I can’t do it any more. I can’t live it any more. You’re the man now..

‘Those words didn’t quite sit well with me. I didn’t feel I was ready to hear those words.’

Depp said his mother ‘went into a very deep, dark depression,’ after his father John walked out.

‘One afternoon I had fallen asleep and woke up and walked into the living room and saw my mother very feebly, almost a slow motion, crawl.’ 

‘I knew something was dreadfully wrong. There was drool coming out of her mouth.’ 

‘Front door busted open, my uncle and two paramedics came in and threw her on the gurney and whisked her out the house to get her out the hospital to pump her stomach.

‘She’d swallowed a multitude of pills to try to commit suicide,’ he said.

‘She was a firecracker of a woman but when she got out of hospital the depression was so deep she lived on the couch and weighed about 70 pounds and all that imagery spun into my head. I thought that was a cowardly way for my father to have left.

‘I was deeply upset by that.’