Statins – The Good, the Bad and the Ugly

Many of us find ourselves prescribed one or other of the statins by our GPs nowadays, often as a result of a routine health check.

But are they really necessary, and what are the risks of taking them ?

In this article, we’ll try to explain exactly what the statins are, how they work, and why the medical profession are so keen on prescribing them for us ‘en masse’.

I’ll start with the ‘why’, to try to put the need for these drugs into context….

Our modern diet is rich in carbohydrates and fats, and for many of us with busy lives often takes the form of highly processed ready meals, which also contain a lot of salt. The problem is that this type of ‘challenge’ to our digestive systems on a continuous basis is an issue – our guts, brains and metabolism simply weren’t designed for it.

The explanation for this mismatch is relatively simple. For the vast majority of our evolutionary history, food was scarce, and whatever came along had to be pounced upon and used to the full…otherwise we simply starved. Our digestive systems and metabolism evolved to cope with this ‘boom and bust’ cycle, such that those with the biggest appetites and the best hunting skills got the most food, were best able to make good use of it to keep them and their offspring alive, and were therefore the most likely to survive and reproduce.

The profusion of cheap and calorie-rich food that is now available to us as a result of mass-production and improved storage and transport, is a very recent event in evolutionary terms (effectively only the last 75 years since the end of WW2). We were never designed to live with a continuous surplus of this sort, and our sedentary existence, increasingly spent peering at computer screens for long periods nowadays, merely compounds the problem by not allowing us to ‘burn off’ the excess calories it delivers (neither has it helped our eyesight, with myopia already at epidemic proportions).

One of the most noticeable direct consequences of this excess is another ‘epidemic’… of obesity. This is particularly worrying in that it has also spread to our kids, thus affecting their health prospects. The increasing demand for the new GLP-1 therapies shows that the vast majority of us want to get thinner, but in many cases our appetites are preventing us from doing so without medical help.

Both government and our healthcare professionals are becoming increasingly worried about the problem, not least because of the huge drain on NHS resources that obesity and Type 2 diabetes, and their consequences, present. The increasing number of affected individuals who are signed-off as permanently unfit for work as a result of obesity- and diet-related health conditions also contribute significantly to the benefits bill, which is adversely affecting our economic prospects…..and their mental health.

But there is a less obvious, but more direct threat to our health from our ‘bad’ dietary habits and lifestyles in the form of excess blood lipids.

To explain its significance, and how it happens, let’s first take a look at some basic biochemistry.

We all carry fats around in our blood circulation in various different forms. This is to allow these important energy-rich ‘fuels’ to be moved between the our gut, where the food is absorbed, to the sites where they are either processed and stored, or used to ‘power’ our life processes.

Fats, along with carbohydrates are the principal fuels we all need to stay alive. If we have too much of them in our blood, however, we run the risk of our blood vessels ‘furring up’ with so-called ‘plaques’ of lipid related material. This process is similar to what happens to water pipes and the inside of our kettles in hard water areas, where calcium and other poorly soluble salts in the water precipitate out and coat the inside of our pipes and our heating elements.

If this furring up process is allowed to continue, eventually one or more of our key arteries or veins will become partially or even completely blocked, cutting off the flow of glucose and oxygen to the tissue it supplies. If this happens in the coronary arteries, part of the heart muscle will die, and our heart may stop altogether. If it happens in the brain, it can cause a stroke, with loss of function to the area affected. Both of these events are potentially fatal, and may occur without warning.

Modern diets, unfortunately for us, are rich in the very agents that promote high lipid and glucose levels in the blood, and therefore drive the furring-up process. There is a known strong correlation between high lipid levels and risk of heart attack or stroke; Type 2 diabetes is associated with high glucose levels, and the condition produces blunted responses to a carbohydrate-rich meal, with higher than ideal peak blood glucose levels as a result. Diabetes has many unpleasant consequences, and can result in poor circulation and even loss of limbs and blindness if not treated.

Hence the desire on the part of our clinicians to screen for high blood lipid levels, and recommend therapies to reduce them if they are deemed to be too high. Many of us do have raised lipid levels (the UK population mean for Total Cholesterol is around 6.7 mmol/l, whereas the ideal range adopted by the NHS is 5.0 mmol/l or below). Thus most patients registering with a new GP practice are offered a blood test at which time a lipid profile sample is usually taken. This test may also include a mesurement of HbA1C, which is form of haemoglobin known to give an indication of our ‘exposure’ to glucose over time, and helps the GP assess the risk of our developing Type 2 diabetes.

What do we mean by a lipid ‘profile’, and what is its significance ?

As already mentioned, fats are carried around the bloodstream in various different forms – usually associated with more soluble molecules such as proteins to ensure they are transported efficiently. Cholesterol is an important endogenous precursor of the bile acids involved in digestion, and of steroid hormones such as oestradiol and testosterone. The ‘standard’ lipid profile will measure ‘Total’ Cholesterol, as well as Triglycerides and High- and Low-Density Lipoproteins (HDL and LDL). HDL and LDL are large soluble fat-protein complexes; LDL in particular has a tendency to drive plaque formation and has thus acquired the moniker of ‘Bad’ cholesterol. HDL returns excess cholesterol to the liver for onward processing, so is deemed 'Good' cholesterol. You can see the chemical structures of key lipids in Figure 1; Figure 4 shows how the various lipoproteins interact with our circulation.

If you’ve recently had a lipid profile done, and want to take a look at the results yourself, you should be able to access them through the NHS smartphone app or via SystmOnline (you may need to complete an access request to your GP surgery for access rights). You can check out the data and what it means using the Health.xlsm Excel app, which you can download here. The Excel app also provides interpretation and advice on BMI and blood pressure measurement, and explains what we can all do at home with minimal equipment to monitor our own health. All the figures used by the app are based on NHS recommended values.

If, as is quite likely, you have a total cholesterol value above the idealised threshold of 5.0 mmol/l, and /or a LDL value much above 3.0 mmol/l, you may be recommended to start on one or other of the statins. This is particularly likely to happen if you are deemed to be ‘at high risk’ of cardiac ill-health for other reasons.

What are Statins ?

Statins are a class of drug designed to reduce lipid levels, in particular the ‘bad’ form of blood cholesterol (i.e. LDL). Contrary to what you might expect from their class name, they are not just designed keep them static. They achieve a reduction by altering cholesterol metabolism such that less of it is produced by the liver. To understand this fully, we need to delve into a bit more biochemistry and look at how lipids in our food are absorbed and transported, and how this ties up with how they are used by the body, and ultimately, disposed of. One of the most commonly prescribed statins is Atorvastatin (See Figure 2 for chemical structure).

Human Lipid Metabolism

As discussed, lipids are key to our existence, and serve many functions, not simply acting as fuels to provide us with energy. Lipid metabolism encompasses the digestion, absorption, transport, synthesis, and breakdown of fats to provide energy, and produce structural components for our cells and tissues, and important signalling molecules.

Lipid metabolism involves a complex set of biochemical processes that allow the body to utilize fats from dietary intake or stored fat reserves. Lipids, including triglycerides, cholesterol, fatty acids, and phospholipids (see Figure 3 for structures), serve as energy sources, components of cell membranes and precursors for steroid hormones. The body regulates lipid metabolism tightly so as to maintain energy balance and prevent disorders such as dyslipidemia, fatty liver disease, and cardiovascular disease.

Digestion and Absorption

The metabolic 'process' begins in the digestive tract, where dietary fats are emulsified by bile salts from the liver, increasing the surface area for enzymatic action. Pancreatic lipase hydrolyzes triglycerides into monoglycerides and free fatty acids, while cholesterol esters are de-esterified into free cholesterol. These digestive products form micelles, which transport the lipid products to the intestinal epithelial cells (enterocytes) for absorption into the circulation. Inside the enterocytes, fatty acids and monoglycerides are re-esterified into triglycerides and packaged with cholesterol and proteins into chylomicrons, which enter the lymphatic system before reaching the bloodstream.

Transport and Storage

Because lipids are hydrophobic (i.e. don’t mix with water on their own), they require lipoproteins for effective and safe transport in the blood. Chylomicrons are the ‘first line’ lipoproteins, which facilitate absorption of dietary lipids in the gut, while very-low-density lipoproteins (VLDL) and low-density lipoproteins (LDL) are effectively circulating transporters, which move endogenous triglycerides and cholesterol from the liver to peripheral tissues (Figure 4).

High-density lipoproteins (HDL) mediate reverse cholesterol transport back to the liver for reprocessing. Triglycerides are stored in adipocytes, and in muscle cells, as an energy reserve, while cholesterol is incorporated into cell membranes or used for steroid hormone synthesis. As discussed, LDL is seen as the ‘villain of the piece’ when it comes to blood vessel plaque formation, and is therefore the primary target of statin therapy.

Lipid Breakdown

Stored triglycerides are broken down through lipolysis, releasing free fatty acids and glycerol when energy is needed. Fatty acids undergo beta-oxidation in mitochondria and peroxisomes, producing acetyl-CoA. This enters the citric acid cycle to generate ATP, which is the universal ‘energy currency’ of our cells. During prolonged fasting or carbohydrate restriction, acetyl-CoA can also be redirected to produce ketone bodies in the liver, providing an alternative energy source for the brain, heart and muscles.

Lipid Biosynthesis

Lipogenesis is the synthesis of fatty acids and triglycerides from excess carbohydrates or proteins. This process occurs primarily in the liver and adipose tissue. Cholesterol is synthesized via the mevalonate pathway (Figure 2) and is essential for membrane structure, bile acids, and steroid hormones. Phospholipids are produced for cell membranes and signalling functions.

Regulation and Clinical Significance

Lipid metabolism is regulated by hormones such as insulin, glucagon, and epinephrine, which control lipogenesis, lipolysis, and beta-oxidation. Poor metabolic control can lead to so-called dyslipidemia, characterized by elevated LDL, low HDL, and high triglyceride levels, and this unfortunate combination readily contributes to atherosclerosis and cardiovascular disorders. Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome are also linked to impaired lipid handling and insulin resistance.

Where do the statins fit in ?

Now we’ve looked in more detail at general biochemistry surrounding the way we handle the fats in our diet, we can focus on how statins work. The statins as a drug class are inhibitors of one of the key enzymes in the lipid biosynthesis pathway, HMG CoA reductase. Figure 4 shows a schematic diagram of the various different lipoprotein forms and the way in which their synthesis is achieved in the liver. By inhibiting this key biosynthetic pathway (Figure 3) early on, it is possible to reduce the amount of cholesterol produced by the liver, and hence the amount circulating in the blood, without causing harmful accumulations of other precursors, or affecting other life processes. Provided removal of the lipid products that are produced downstream of the blockage, or via other pathways, continues as normal, the overall level of cholesterol in the blood should decrease as a result of statin therapy.

Therapy, Side Effects and Treatment Programs

Statins, once prescribed, are generally taken long-term or until treatment is discontinued for a specific reason. To maintain lower blood levels of Total cholesterol and LDL, a steady level of the drug is needed to keep the enzyme blockage in place; if we stop taking it, there is a risk that lipid levels will rise again.

All drugs produce side effects if taken in sufficient quantities, and statins are no exception. The objective of therapy for any drug is to minimise the side effects while maximising the benefits of the drug. The statins, by interfering with a key step in lipid metabolism, do have some significant side effects, ranging from common mild and transient ones such as headache and effects on gut motility to (fortunately) much rarer ones such as severe allergic reactions and severe muscle damage. You’ll find a full list of side effects and reactions in the product leaflet supplied with each pack. With statins, side effects are often transitory, and disappear as the body adapts to the new therapeutic challenge.

Clinicians will normally start patients on a low dose (typically 10 mg for Atorvastatin) and work upwards, while monitoring for side effects early on in the treatment program and testing for changes in lipid profiles over time (usually at 1 month and 3 months post first dose) to ensure the medication is actually doing the job, and is well-tolerated. The side effect profiles for different statins do vary, so in the event of Atorvastatin presenting with tolerability issues early on, there is also scope for switching to other statins. When starting a statin for the first time, it’s wise to start with the lowest possible dose and work upwards, to ensure any serious side effects are picked up early. If you do encounter problems when starting treatment, always report them to a pharmacy or your GP, and if necessary stop taking the medication while seeking advice.

The Importance of Dietary Control

One of the problems that emerges when a patient is prescribed statins after a sustained period spent attempting lipid lowering via dietary restrictions alone is the ‘relaxation effect’. There is a temptation, once on therapy, to resume one’s old ‘bad’ dietary habits, which were probably at least partly responsible for the high lipid burden. The reasoning given is typically “..the statins will keep my cholesterol low whatever I eat, won't they, so I can have what I want now..”.

This is, unfortunately, a misunderstanding of the power of statins to ‘cure all dietary ills’. They can’t, and we shouldn’t expect them to. They will only work properly if we maintain a ‘sensible’ balanced diet with minimal exposure to highly processed foods and plenty of fruit, vegetables and other roughage-containing foods. This admittedly rather disappointing reality does generate other benefits, though. A balanced diet won’t just improve our heart and circulatory health by preventing the effects of atherosclerosis, but will help control obesity and help maintain healthy blood sugar levels, both of which contribute to development of Type 2 diabetes and all its ills.

The harsh reality in all this is that if you want a longer life with minimal ill-health, particularly in your final years, a sensible diet and control over blood glucose and lipid levels is a must.

Non-dietary alternatives to Statins

If for some reason you’re unable to tolerate effective doses of one or other of the statins, and find it impossible to reduce your lipid levels by dietary control alone (as unfortunately do many people who try it) all is not lost. Here is a brief list of the alternative options:

* Ezetimibe (Zetia) – Reduces cholesterol absorption in the small intestine, lowering LDL by about 20% and can be combined with other therapies for greater effect

* Bempedoic Acid (Nexletol) – Works in the liver to reduce cholesterol production, lowering LDL by 20–25% with fewer muscle-related side effects than statins.

* Combination Pills – Ezetimibe with bempedoic acid (Nexlizet) or with simvastatin (Vytorin) can reduce LDL by 40–60%.

* PCSK9 Inhibitors – Injectable drugs like alirocumab (Praluent), evolocumab (Repatha), and inclisiran (Leqvio) enhance liver clearance of LDL cholesterol, offering substantial reductions, especially for familial hypercholesterolemia.

* Bile Acid Sequestrants – Medications such as cholestyramine bind bile acids in the gut, prompting the liver to convert more cholesterol into bile acids, lowering LDL levels that way.

* Fibrates – Drugs like gemfibrozil primarily lower triglycerides but can modestly affect LDL and HDL cholesterol.

Please note that most if not all of these are prescription medicines in UK, so will need to be discussed with your GP before you can obtain them.

Final Thoughts

In this review of statins, we’ve tried to explain how statins can be used as a ‘therapeutic management tool’ to keep our lipid profiles healthy and prevent serious damage to our blood vessels, with all that implies. We’ve also looked at some basic biochemistry, to provide the background for explaining how the statins actually work.

We’re all living longer, and we really need to be more proactive in managing our own health – the lack of availability of GP appointments isn’t likely to be remedied soon, so the more we can do to prevent chronic illness, and the need to see our GPs, the better. There’s a lot we can do to monitor our own health – take a look at the Excel app, which you can download using the link above, to find out more about what you can do at home, and how to interpret your GP test results.

First published: 22.7.26

Figure 1: Chemical Structures of Key Lipids