If you are taking a statin to lower your cholesterol, you may benefit from taking coenzyme Q10 supplements, too, as statins block the production of both cholesterol and coenzyme Q10 in the liver. Coenzyme Q10 is a vital nutrient for energy production in cells, especially muscle and heart cells, and coenzyme Q10 deficiency may account for some of the muscle-related side effects associated with statin medication.
How statins work
Statins (atorvastatin, fluvastatin, lovastatin, pravastatin, pitavastatin, rosuvastatin, simvastatin) are widely prescribed to reduce cholesterol production in cells, and are offered to anyone whose risk of a heart attack or stroke over the next ten years is at least 10%.
Statins block an enzyme, HMG-CoA reductase, in the first step of a series of chemical reactions known as the mevalonate pathway, as shown on the right.
By blocking this step, the production of all products further down in this pathway are reduced – you make less cholesterol, but you also make less coenzyme Q10. Data from 8 clinical trials confirm that taking a statin significantly lowers blood coenzyme Q10 concentrations and is greatest in those taking statins for at least 12 weeks.
In fact, statins are so effective they can halve your circulating blood levels of coenzyme Q10 within two to four weeks of starting treatment.
Coenzyme Q10 is the ‘spark plug’ of oxygen processing
Coenzyme Q10 is vital for oxygen processing and is often described as the spark plug of energy production.
Coenzyme Q10 is vital for energy production within your cells’ powerhouses, the mitochondria. Tissues containing the most mitochondria therefore have the highest need for coenzyme Q10.
Red blood cells contain no mitochondria – otherwise they would use up the oxygen they carry – but a typical heart muscle cell contains 5000 or more mitochondria to supply the energy for continuous contraction.
A skeletal muscle cell in your thigh typically contains around 2000 mitochondria, but these increase in number and size according to the amount of exercise you take. A muscle cell from an Olympic athlete may contain as many as 4000 mitochondria or more. Organ cells, such as those in the liver, brain and pancreas, are also well supplied to fuel their hard work.
When you take a statin, and your coenzyme Q10 production is typically halved, some cells may not generate all the energy-rich molecules they need and function at a sub-optimal level.
Lack of coenzyme Q10 affects muscle cells the most and is associated with symptoms such as aches and pains (myalgia), weakness (myopathy) and exercise intolerance.
When low levels of coenzyme Q10 affect heart muscle contraction, deficiency can lead to heart pump failure. Taking coenzyme Q10 supplements may improve the strength of heart muscle contraction.
Statins and muscle side effects
Biopsies from statin-treated patients frequently show low muscle levels of coenzyme Q10. In cell cultures, statins are associated with poor mitochondrial function and reduced oxygen consumption. The fact that statins lower coenzyme Q10 levels may account for the muscle-associated side effects that occur in some people, especially those taking high doses.
Between 5% and 10% of people taking a statin develop muscle aches and pains (myalgia) or weakness (myopathy). A few patients develop a rare condition called rhabdomyolysis, in which muscle fibres break down. This is a serious condition which can lead to heart failure and kidney problems if not diagnosed promptly and the statin stopped.
These potential problems are not a new understanding. They were recognised in a pharmaceutical patent filed as long ago as 1990 for a statin plus coenzyme Q10 combination to counteract statin-associated skeletal muscle myopathy. Quite why this patent was never acted on remains a medical mystery!
Statins and type 2 diabetes
A UK study, involving over two million people, found that statins increased the risk of developing type 2 diabetes by 57% over a five-year, follow-up period. One reason suggested to explain this increased risk is that reduced levels of coenzyme Q10 might affect insulin hormone production within pancreas cells, or the inability of muscle and fat cells to respond to insulin.
Statins and memory impairment
Several studies suggest that taking a statin might affect your ability to think straight. A recent US study, involving over 482,000 statin users plus the same number of matched non-users, found that those taking a statin were four times more likely to experience acute memory loss than non-users. Symptoms were experienced within 30 days of starting treatment. As brain cells contain high numbers of mitochondria, it’s possible that memory-associated side effects are related to a sudden reduction in coenzyme Q10 levels.
Coenzyme Q10 supplements for statin muscle side effects
Statins are now used by hundreds of millions of people every day, of which at least one in twenty will develop muscle-related side effects which could cause them to stop taking their medication. Given the potential size of the problem, it’s astonishing that so few trials have investigated whether or not coenzyme Q10 supplements can help patients stay on their medication by preventing or reducing adverse events. The trials that have been published involve too few patients to sway current prescribing guidelines.
In one study, 18 people with statin-related muscle pain received 100mg/day coenzyme Q10 and 14 received vitamin E. Pain reduced by 40% in those receiving coenzyme Q10 compared with a 9% increase in pain in those not taking coenzyme Q10. The authors concluded that ‘… coenzyme Q10 supplementation may offer an alternative to stopping treatment with these vital drugs.’
A second study, involving 60 people with statin-associated myopathy, found that coenzyme Q10 supplements reduced the intensity of muscle pain by 53%, muscle weakness by 60% and muscle cramps by 65%, while tiredness decreased by 82%. No significant changes occurred in the placebo group.
Three other, similarly small studies did not show a benefit, however. A meta-analysis of pooled data from the 253 people in these five trials (2 of which were positive, 2 neutral and 1 negative) found that taking coenzyme Q10 supplements decreased muscle pain, on average, by 53%. This may sound good but, because of the low number of patients involved, this result was not statistically significant. Even so, the overall trend is towards favouring coenzyme Q10 as shown by the brown diamond below (Derived from Banach et al 2015).
Another small trial, whose results were not available for inclusion in the above meta-analysis, involved 50 patients with statin-related muscle pain who received either 100mg coenzyme Q10 daily or placebo.
In those taking coenzyme Q10, pain decreased in 75% of patients, with the Pain Severity Score reducing by 33% overall. In those taking placebo, pain levels showed no significant change.
One criticism raised about the above meta-analysis is that the doses of coenzyme Q10 used may not have been high enough to reduce muscle pain for all patients.
In the meta-analysis, the authors explained that ‘the human body contains about 2g of coenzyme Q10, of which 500mg must be replaced each day’ by diet or by its synthesis in body cells.
Coenzyme Q10 is found in all animal and plant foods, but the main dietary sources are meat and offal.
Average daily intakes of coenzyme Q10 are estimated as up to 5mg for meat eaters and just 1mg for those eating a plant-based diet. If cell synthesis of coenzyme Q10 is severely depleted by a high dose statin, then some patients may need up to 500mg supplements per day to replenish the short fall. This was before the availability of the more potent, reduced form of coenzyme Q10, known as ubiquinol, which is taken at a dose of 100mg per day.
Disappointing results for coenzyme Q10
Unfortunately, a trial set up to test larger doses of 600mg coenzyme Q10 per day, published in February 2015, produced unexpectedly negative results. A group of 120 patients with previously diagnosed muscle pain (severe enough to stop taking a statin) were re-challenged with either a statin or a placebo. Of those re-challenged with the statin, only 36% (41 patients) re-developed muscle pain.
These 41 patients were asked to continue the statin and to also take either an inactive placebo or 600mg coenzyme Q10 (so a good dose, overcoming the previous objections that trial doses were too low). These supplements were taken for two weeks, to provide a loading dose, then continued for another eight weeks, or until symptoms had persisted for one week or became intolerable, at which point the patient withdrew from treatment.
Only 24 patients completed this part of the study. These were asked to cross over to the other supplement (so from placebo to coenzyme Q10 and vice versa) after a four-week ‘wash-out’ period. Disappointingly, the Pain Severity Scores increased with continuing statin therapy – whether or not they were taking high dose coenzyme Q10 or placebo.
As so few patients progressed to the final part of this trial, these disappointing results could be due to the low numbers involved. One possibility is that the muscle pains in these people were associated with a vitamin D deficiency, as statins reduce the cholesterol-like building blocks needed to initiate the synthesis of vitamin D in the skin on exposure to sunlight.
Even so, this new evidence underlines the fact that everyone is different, and not everyone will respond to an intervention that others have found helpful. The only way to know for sure whether or not a coenzyme Q10 supplement will prevent or reduce a statin side effect for you is to take them for a trial period of, for example, three months. The usual recommended dose is 100mg ubiquinol coenzyme Q10, which is equivalent to 280 mg of the ubiquinone form of coenzyme Q10.
Coenzyme Q10 is an antioxidant
Coronary heart disease is associated with chronic inflammation within artery walls, which hastens the hardening and furring up process of atherosclerosis. As coenzyme Q10 is a powerful antioxidant, taking a statin lowers one of the body’s natural, anti-inflammatory defences. Some researchers even claim that taking statins may therefore stimulate arterial damage and atherosclerosis, although this is highly controversial.
Coenzyme Q10 is prescribed to treat some types of heart disease, especially heart failure. Researchers therefore investigated its effects against coronary heart disease in 51 patients with severe narrowing of one major coronary artery (50% stenosis). All participants were already on a statin, and therefore had suppressed coenzyme Q10 levels.
Participants were divided into two groups, one of which took coenzyme Q10 supplements (150mg ubiquinone twice a day) while the other took inactive placebo for 12 weeks.
In those taking the coenzyme Q10 supplements, circulating blood levels of coenzyme Q10 increased five-fold within four weeks of starting treatment. Levels of antioxidant enzymes and inflammatory chemicals were measured before and after the intervention, and antioxidant activity was significantly higher and the level of inflammatory markers was significantly lower in those who had taken coenzyme Q10.
Raised levels of inflammatory markers (eg TNF-α, IL-6) are strongly associated with an increased risk of heart attack and death. Coenzyme Q10 supplements may therefore play an additional protective role in the heart by reducing inflammation in addition to its vital role in generating energy for heart muscle contraction.
Statin use is increasing
Initially, statins were prescribed only for people at high risk of coronary heart disease and stroke who also had a raised cholesterol level. Now they are offered to all people whose risk of a heart attack or stroke over the following ten years is assessed as 10% or greater. This assessment is calculated from factors such as your age, sex, body mass index, ethnicity, smoking status, family history and whether or not you have diabetes. You can calculate your own risk via the QRISK website. It helps to know your systolic blood pressure and cholesterol/HDL ratio but these are not essential.
The increased use of statins is based on evidence that they reduce your risk of a heart attack and premature death. By how much?
- If 100 people with a cardiovascular risk of 10% over 10 years take a statin, then 4 people will be saved from developing coronary heart disease or having a stroke. The benefits increase in line with a rising risk assessment.
Will taking a statin help you live longer?
- One professor of statistics from the Medical Research Council has apparently calculated that taking a statin will let you live, on average, three months longer than if you hadn’t taken the statin.
In the UK, the National Institute for Health and Care Excellence (NICE) has produced a patient decision aid to help you decide whether or not to take a statin, which can be viewed HERE.
If you take a statin, you may benefit from coenzyme Q10
If you stop taking a statin that is medically indicated, your risk of a heart attack or stroke may increase. Some people who stop taking a statin do so because they experience unacceptable side effects. The medical approach to these side effects is to see if you can tolerate a reduced dose, a switch to another statin, or even taking a statin on alternate days. Another approach is to see if taking a coenzyme Q10 supplement could help you tolerate the statin better. It won’t work for everyone, but coenzyme Q10 is one of the safest supplements available with few reported side effects.
According to the US-based Journal of Family Practice, coenzyme Q10 supplements are the only treatment that has shown promise in treating statin adverse effects such as muscle symptoms. Although studies are small, and produced mixed results, the overall evidence suggests that coenzyme Q10 can decrease the development or severity of symptoms. Importantly, taking coenzyme Q10 supplements has been shown to maintain blood levels of coenzyme Q10 without affecting the cholesterol-lowering effect of the statin medication.
Given that coenzyme Q10 has such important actions in the body, I believe it’s worth raising blood levels of this energy-boosting antioxidant back to the normal range in everyone taking a statin (as that original patent suggested) – even if statin side effects are absent. Not everyone agrees, so do check with your doctor first. It’s also advisable to take a vitamin D3 supplement as vitamin D is make in the body from cholesterol and when statins lower cholesterol, they also lower vitamin D3 production. Lack of vitamin D has also been associated with muscle side effects.
The best coenzyme Q10 dose
Coenzyme Q10 supplements are available in two forms, as ubiquinol and ubiquinone.
Ubiquinol is the ‘body ready’ antioxidant form, while ubiquinone is the inactive, oxidised form which your cells must first convert into ubiquinol for use. If you are taking a statin, the ubiquinol form is best.
The usual recommended dose of ubiquinol is 100mg per day.
Ubiquinone has the advantage of being cheaper, but is less readily absorbed and used by cells, so a higher dose of 200mg per day is usually advised if you are on a statin. This can be taken in one go, or divided into two daily doses of 100mg if you prefer. Some experts recommend increasing the dose to 400mg if the lower dose doesn’t work, or if you are on a high statin dose.
As coenzyme Q10 is oil-soluble, take softgel capsules (in which the coenzyme Q10 is dissolved in oil) to maximise absorption (ie avoid solid tablets). Always look for supplements that are made to a pharmaceutical standard known as GMP (Good Manufacturing Practice) to ensure each capsule provides a consistent dose.
Side effects relating to coenzyme Q10 are uncommon. Occasional and transient, mild nausea has been reported at high doses (usually 600mg per day or more, used in clinical trials to treat hypertension).
So there you have it. My take on the current state of affairs relating to statins and coenzyme Q10. The evidence of benefit against muscle-related statin side effects is not as strong as I would like, as no-one has yet funded and published large-scale trials. However, given the important role of coenzyme Q10 in the body, it seems sensible to replenish levels of this vitamin-like compound back up to the range that nature intended.
There is also increasing evidence that vitamin D supplements are important for people who are taking statin medication.
NB If you experience severe muscle pain or weakness while taking a statin, contact your doctor immediately. You may need tests to assess your muscle health, and your statin switched to an alternative version, or a lower dose.
Click here to read my Expert Health Review on the best co-enzyme Q10 supplement brands.
Have you experienced statin side effects or found coenzyme Q10 helpful? Do share your experiences in the comments below.
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