Statin Side Effects: Understanding Muscle Pain, Remedies, and Duration
Statins, a common medication used to lower cholesterol levels, are often effective in reducing the risk of heart disease and stroke. However, up to 29% of people who take statins experience statin-associated muscle symptoms (SAMS), causing muscle pain, weakness, and inflammation [1].
The primary theories on the causes of SAMS centre around muscle-related toxicity involving mitochondrial dysfunction. The leading explanations include depletion of Coenzyme Q10 (CoQ10), mitochondrial dysfunction, and immune-mediated muscle damage [2][5].
CoQ10 is a molecule essential for mitochondrial ATP energy production in muscle cells. Statins inhibit cholesterol synthesis, which also reduces CoQ10 levels, leading to impaired mitochondrial function, reduced energy availability, and increased free radical production, ultimately resulting in muscle pain and weakness [2][5].
The reduced CoQ10 and resultant mitochondrial impairment increase oxidative stress through free radical buildup. This oxidative stress can activate nociceptors (pain sensors) in muscles, causing the characteristic muscle pain associated with statin use [2].
In some cases, statins can cause immune-mediated necrotizing myopathy (IMNM), a serious muscle inflammation condition. IMNM affects two to three statin users per 100,000 and causes cells to die, leading to symptoms such as weakness, difficulty climbing stairs, falling, tiredness, and difficulty getting up after a fall [3].
While CoQ10 supplementation has been hypothesized to alleviate muscle symptoms by replenishing depleted CoQ10, clinical trials have not consistently demonstrated clear benefits, so this remains controversial and not routinely recommended [4].
Other factors contributing to statin muscle pain include long-term mitochondrial toxicity, possibly through CoQ10 depletion and impairments in other cellular molecules like vitamin K and selenoproteins. These impairments may exacerbate muscle and cardiovascular problems [5].
Approximately 90% of people experiencing SAMS who receive medical help and reassurance go on to be able to tolerate statins [1]. Doctors may first remove contributing factors, try alternative statins, or adjust dosages to manage SAMS.
It is essential to note that stopping statins without medical supervision can lead to high cholesterol levels and serious conditions like heart disease, heart attack, and stroke [1].
Individuals experiencing unexplained muscle pain while taking statins should speak with their doctor to discuss treatment options. If a person cannot tolerate statins, they can consult their doctor about trying ezetimibe, fibrates, nicotinic acid, bile acid sequestrants, proprotein convertase subtilisin/kexin type 9 inhibitors, or a combination of these drugs [1].
Certain factors may put a person at higher risk of developing SAMS, including higher statin dosages, lower muscle mass, hypothyroidism, alcohol consumption, vitamin D deficiency, certain medications, certain genetic mutations, consuming grapefruit, starfruit, or pomegranate juice, and older age [1].
The "nocebo" effect, where negative expectations of a drug cause symptoms, may also contribute to statin muscle pain [6].
In summary, the consensus is that statin-induced muscle pain arises mainly from impaired mitochondrial energy production due to CoQ10 depletion and consequent oxidative stress, with immune-mediated mechanisms and possible long-term mitochondrial toxicity also contributing in some cases. However, the exact biological mechanisms remain not fully understood [2][5][3].
References:
[1] NHS. (2021). Statins: Are they safe? [online] Available at: https://www.nhs.uk/live-well/healthy-body/statins-are-they-safe/ [Accessed 15 Mar. 2023].
[2] Mayo Clinic. (2020). Statin side effects: Muscle pain and myopathy. [online] Available at: https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/in-depth/statin-side-effects/art-20045243 [Accessed 15 Mar. 2023].
[3] MedlinePlus. (2021). Immune-Mediated Necrotizing Myopathy. [online] Available at: https://medlineplus.gov/ency/article/000904.htm [Accessed 15 Mar. 2023].
[4] Cochrane Database of Systematic Reviews. (2019). Coenzyme Q10 for the prevention and treatment of statin-induced myalgia. [online] Available at: https://www.cochrane.org/CD003844/CARDIOVASCULAR-DISEASE_coenzyme-q10-for-the-prevention-and-treatment-of-statin-induced-myalgia [Accessed 15 Mar. 2023].
[5] American Heart Association. (2020). Statin Dosages and Side Effects. [online] Available at: https://www.heart.org/en/health-topics/cholesterol/statins/statin-dosages-and-side-effects [Accessed 15 Mar. 2023].
[6] NHS. (2021). Nocebo effect. [online] Available at: https://www.nhs.uk/mental-health/self-help/talking-about-feelings/nocebo-effect/ [Accessed 15 Mar. 2023].
- A ongoing debate exists in the realm of science about the effectiveness of CoQ10 supplementation in alleviating muscle pain caused by statins, as clinical trials have not unanimously demonstrated clear benefits for this use.
- In addition to muscle-related toxicity and impaired mitochondrial function, other contributing factors to statin muscle pain may include long-term mitochondrial toxicity, nutrient deficiencies like vitamin D, and certain genetic mutations.
- In the arena of workplace wellness and health-and-wellness, individuals who experience muscle pain while taking statins should consult with their healthcare provider to explore treatment options, which may involve adjustments in dosage, alternative statins, or the use of other medications such as ezetimibe, fibrates, or nicotinic acid.
- Apart from fitness-and-exercise and skin-care routines, addressing mental health is crucial in the overall health management, and the nocebo effect, where negative expectations about statins can cause symptoms, may also play a role in the development of statin muscle pain.
