Statins: a natural discovery from fungi, and why they still matter
Many patients who are interested in natural therapies are surprised to learn that one of the most important modern heart medications has its origins in nature — specifically in fungi.
The story begins with Professor Akira Endo, a Japanese biochemist who died in 2024 at the age of 90. Endo had a lifelong interest in fungi and moulds. In the early 1970s, while working in Japan, he screened thousands of fungal extracts looking for a substance that could block cholesterol production. His work led to the discovery of the first statin, compactin, from a Penicillium mould.
There is a strong historical parallel with the discovery of penicillin. Alexander Fleming observed that a Penicillium mould could kill bacteria. Endo, decades later, discovered that another fungal product could inhibit cholesterol production. In both cases, careful observation of nature led to a major medical advance.
This is worth remembering because statins are sometimes seen as “unnatural” drugs. In fact, the first statins came directly from a natural source. Modern statins are more refined, reliable and carefully dosed, but their origin is very much in the natural world.
Why take a statin?
Statins reduce LDL cholesterol, often called “bad cholesterol”. LDL cholesterol is one of the main drivers of plaque build-up in arteries. These plaques can gradually narrow blood vessels, but they can also rupture suddenly and cause a clot, leading to a heart attack or stroke.
Statins help in several ways. They lower LDL cholesterol, reduce inflammation within plaques, and help stabilise plaques so they are less likely to rupture. This plaque-stabilising effect is one of the reasons statins are so important in preventing heart attacks and strokes.
One of the challenges in preventive medicine is that coronary artery disease can be silent. A person may feel well and still have significant plaque in the heart arteries. For some people, a heart attack or sudden cardiac death is the first sign that they had coronary artery disease.
This is why cardiovascular risk assessment matters, particularly for men over 50 and for people with risk factors such as high blood pressure, diabetes, borderline diabetes, smoking history, family history of premature heart disease, or raised cholesterol.
A coronary artery calcium score is a very useful test in selected patients. It is a CT scan that measures calcified plaque in the coronary arteries. It does not require dye and is usually quick. A score of zero is reassuring, while a higher score suggests a greater plaque burden and a higher future cardiovascular risk. It can be especially helpful when deciding whether a statin is appropriate in someone whose risk is not obvious from cholesterol numbers alone.
The death of Shane Warne at age 52 made many Australian men think about their own heart risk. I do not know his personal medical history and it would not be appropriate to speculate. However, his death is a reminder that middle-aged men, even those who appear active or well, should not ignore cardiovascular risk assessment. In some people, earlier detection of coronary plaque may lead to preventive treatment that changes the outcome.
What is a meta-analysis?
A meta-analysis is a study that combines results from multiple previous studies. Rather than relying on one trial alone, researchers pool data from many trials to get a clearer and more reliable answer.
A particularly strong type is an “individual participant data meta-analysis”. Instead of just using the summary results from each trial, researchers analyse the original data from individual participants. This allows more precise assessment of benefits and side effects.
The latest major statin safety paper, published in The Lancet, looked at adverse effects listed in statin product information. This is important because product information leaflets can list many possible symptoms, but not all of them are necessarily caused by the medication.
The researchers analysed data from large double-blind randomised controlled trials. “Double-blind” means that neither the patients nor the treating doctors knew who was taking the statin and who was taking placebo. This is important because many symptoms — tiredness, aches, poor sleep, headache, memory concerns, nausea, low mood — are common in the general population. If they occur just as often in people taking placebo, it suggests they may not be caused by the statin itself.
The Lancet analysis found that most side effects listed in statin product information were not clearly caused by statins when tested properly in blinded trials. In particular, the evidence did not support statins causing most of the listed problems such as cognitive impairment, depression, sleep disturbance or peripheral neuropathy.
This does not mean statins have no side effects. It means the true risks appear to be smaller and more specific than many people fear.
Real side effects still matter
The balanced message is that statins are generally very well tolerated, but they are not side-effect free.
The best-known issue is muscle pain or, much more rarely, true muscle inflammation or injury. If a patient develops new muscle aching, weakness or tenderness after starting or increasing a statin, a blood test called creatine kinase, or CK/CPK, can help check for muscle inflammation.
However, CK testing is usually most useful when symptoms are present. In a patient without muscle symptoms, routine CK monitoring is not usually necessary. Also, if a patient has mild symptoms but has a strong cardiovascular reason for taking a statin, it is not always necessary to stop or reduce the medication immediately. The decision depends on the severity of symptoms, CK level, cardiovascular risk and patient preference.
Statins can also slightly increase blood glucose and HbA1c. In most people this is small. However, in someone with diabetes, borderline diabetes, or a strong family history of diabetes, it is worth being aware of. In some patients already close to the diabetes threshold, a statin may bring forward a diagnosis of diabetes. This does not usually outweigh the cardiovascular benefit, but it does mean HbA1c should be monitored sensibly.
The latest Lancet meta-analysis also found small increases in some liver blood test abnormalities, but not an increase in serious liver disease such as liver failure or hepatitis. This supports the usual clinical approach: check liver tests when starting or adjusting treatment, but do not assume that every minor abnormality means the medication must be stopped.
What about tendonitis?
Tendonitis is less well known than muscle symptoms. It is also less clearly established. There are case reports and observational concerns about tendon pain or tendon injury in some people taking statins, but the evidence is not as strong as it is for rare muscle injury.
Still, in a patient with ongoing or unexplained tendonitis — especially if symptoms began after starting a statin or increasing the dose — it is reasonable to review the timing, consider other causes, and discuss whether a dose reduction, change of statin, or temporary trial off the medication is appropriate.
This should be individualised. Patients should not stop a statin abruptly without discussing it, particularly if they have known coronary disease, a previous heart attack or stroke, diabetes, a high calcium score, or other significant cardiovascular risk.
Which statin?
My personal preference is often rosuvastatin. It is potent, convenient, and in my clinical experience often well tolerated. It can achieve a strong LDL reduction at relatively low doses. Some patients who have not tolerated one statin may tolerate another, so it is worth individualising treatment rather than assuming “all statins are the same”.
The best statin is the one that achieves the risk reduction needed and that the patient can comfortably continue long term.
Natural does not mean unscientific
For patients interested in natural therapies, the history of statins is a useful reminder that “natural” and “medical” are not opposites.
Penicillin came from mould. Statins came from fungi. Many important treatments began with observations from nature. The real question is not whether a treatment is natural or synthetic, but whether it is safe, effective, appropriate for the individual patient, and monitored carefully.
Statins are not needed by everyone. But for patients with increased cardiovascular risk, known plaque, diabetes, a high coronary calcium score, or previous cardiovascular disease, they remain one of the most important preventive treatments available.
The aim is not simply to lower a number on a blood test. The aim is to reduce the chance of heart attack, stroke and sudden death.
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