According to websites of pharmaceutical companies, the statin atorvastatin ‘occasionally’ causes side effects such as ‘muscle pain, joint pain, muscle weakness and muscle cramp’. ‘Very occasionally’ these side effects may be a sign of serious muscle damage. A Japanese animal study suggests that supplementation with the co-enzyme Q10 can make a positive difference in these cases.
Statins such as atorvastatin – the active ingredient in Pfizer’s Lipitor – inhibit the enzyme HMG-CoA-reductase, thus reducing the synthesis of cholesterol in the body. The result is a considerable decrease especially in the amount of ‘bad cholesterol’ LDL in the body, and a dramatic reduction in the likelihood of having a heart attack. But because HMG-CoA is an important enzyme, statins inhibit a lot more too.
For example, they reduce the production of ubiquinone, alias Q10, a co-enzyme that plays a vital role in the mitochondria of muscle cells. The chemical structure of Q10 is shown on the right. The muscle pain and damage that ‘occasionally’ occurs in statin takers may well be connected to the decrease in the amount of Q10, researchers suspect.
The theory that statins can reduce the production of Q10 in some people to dangerously low levels is not new. Merck developed the theory in the 1980s, and in 1989 filed a patent application for a medicine that contained Q10 and statins. [US 4929437 A]
But nevertheless… Theories are alright, but proof that confirms theories is even better. That’s why we admire the animal study that Ayako Muraki of Keio University in Japan published recently in the Journal of Applied Physiology.
Young male rats were given atorvastatin or pravastatin, another statin.
Half of both groups of mice were also given Q10 in their drinking water. The human equivalent of the dose they used would be 200 mg ubiquinone per day. If you were to use a form of Q10 that is more easily absorbed the dose would be considerably lower.
After eight weeks the researchers got the mice to run to the point of exhaustion. Pravastatin [structural formula on the right] had no effect on the mice’s endurance capacity; atorvastatin did reduce the total running distance. Atorvastatin also reduced the amount of muscle mass, but the effect was not statistically significant.
Atorvastatin sabotages the work that the mitochondria do, and reduces the amount of Q10 the Japanese discovered.
In the mice that were given Q10 as well as atorvastatin there was almost no reduction in endurance capacity. The amount of Q10 in the muscles didn’t decrease and the mitochondria activity level remained high.
“The findings of the present study provide the scientific and mechanistic basis for co-enzyme Q10 supplementation to statin users”, the researchers conclude.
Coenzyme Q10 reverses mitochondrial dysfunction in atorvastatin-treated mice and increases exercise endurance.
Statins are cholesterol-lowering drugs widely used in the prevention of cardiovascular diseases; however, they are associated with various types of myopathies. Statins inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and thus decrease biosynthesis of low-density lipoprotein cholesterol and may also reduce ubiquinones, essential coenzymes of a mitochondrial electron transport chain, which contain isoprenoid residues, synthesized through an HMG-CoA reductase-dependent pathway. Therefore, we hypothesized that statin treatment might influence physical performance through muscular mitochondrial dysfunction due to ubiquinone deficiency. The effect of two statins, atorvastatin and pravastatin, on ubiquinone content, mitochondrial function, and physical performance was examined by using statin-treated mice. Changes in energy metabolism in association with statin treatment were studied by using cultured myocytes. We found that atorvastatin-treated mice developed muscular mitochondrial dysfunction due to ubiquinone deficiency and a decrease in exercise endurance without affecting muscle mass and strength. Meanwhile, pravastatin at ten times higher dose of atorvastatin had no such effects. In cultured myocytes, atorvastatin-related decrease in mitochondrial activity led to a decrease in oxygen utilization and an increase in lactate production. Conversely, coenzyme Q(10) treatment in atorvastatin-treated mice reversed atorvastatin-related mitochondrial dysfunction and a decrease in oxygen utilization, and thus improved exercise endurance. Atorvastatin decreased exercise endurance in mice through mitochondrial dysfunction due to ubiquinone deficiency. Ubiquinone supplementation with coenzyme Q(10) could reverse atorvastatin-related mitochondrial dysfunction and decrease in exercise tolerance.
PMID: 22653988 [PubMed - indexed for MEDLINE]