Statins, fibrates and beta blockers increase fatigue during moderate intensity exercise

This study was published in the British Journal of Clinical Pharmacology 1997 Mar;43(3):291-300

 

Study title and authors:

The effects of combined treatment with beta 1-selective receptor antagonists and lipid-lowering drugs on fat metabolism and measures of fatigue during moderate intensity exercise: a placebo-controlled study in healthy subjects.

Eagles CJ, Kendall MJ.

Department of Medicine, Queen Elizabeth Hospital, Edgbaston, Birmingham, UK.

 

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/9088584

This study examined the effects of different combinations of beta blockers (metoprolol and atenolol) and cholesterol-lowering drugs (fluvastatin and bezafibrate), on fatigue during moderate intensity exercise in healthy young volunteers. The study included 14 healthy men and women, average age 21.9 years, who completed five, 90 minute walks after been treated with either four different combinations of metoprolol or atenolol and fluvastatin or bezafibrate, or placebo.

The study found:
(a) Fat oxidation was between 24% to 40 % lower in subjects treated with beta blockers and cholesterol lowering drugs compared to subjects on placebo. 
(b) Ammonia levels were between 51% to 170 % higher in subjects treated with beta blockers and cholesterol lowering drugs compared to subjects on placebo. (High ammonia levels can lead to lack of energy and brain damage).
(c) Scores on the feeling scale were significantly lower in subjects treated with beta blockers and cholesterol lowering drugs compared to subjects on placebo. (i.e. subjects treated with beta blockers and cholesterol lowering drugs felt worse compared to subjects on placebo).
(d) Subjects treated with beta blockers and cholesterol lowering drugs found it took between 12% to 40% more perceived cardiorespiratory effort to complete the walks compared to subjects on placebo.
(e) Subjects treated with beta blockers and cholesterol lowering drugs found it took between 22% to 40% more perceived leg effort to complete the walks compared to subjects on placebo.
(f) Subjects treated with beta blockers and cholesterol lowering drugs suffered 22% to 45% more perceived leg pain compared to subjects on placebo.

In healthy volunteers, this study revealed that combinations of beta blockers and cholesterol lowering drugs were associated with increased fatigue during moderate intensity exercise.

Doctor says statin drug hypersensitivity reactions are potentially life-threatening

This paper was published in Chest 1999 Mar;115(3):886-9

Study title and authors:
Polymyalgia, hypersensitivity pneumonitis and other reactions in patients receiving HMG-CoA reductase inhibitors: a report of ten cases.

Liebhaber MI, Wright RS, Gelberg HJ, Dyer Z, Kupperman JL.
Department of Medicine and Pediatrics, UCLA School of Medicine, Los Angeles, CA, USA. mil1258@pol.net

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/10084510

 
This paper, headed by Dr Myron Liebhaber from the University of California Los Angeles School of Medicine, describes ten patients who developed hypersensitivity-type reactions after taking statin medications. (A hypersensitivity reaction is an exaggerated inflammatory response by the immune system to a drug or other foreign substance).
 
Patient 1
(i) Nine months after starting lovastatin, 20 mg daily, a 54 year old man developed urticaria over his entire body and angioedema of his upper lip. (Urticaria also known as hives, is a kind of skin rash with pale red, raised, itchy bumps. Angioedema is swelling under the skin).
(ii) Tests revealed an autoimmune disorder (where the body attacks its own tissues).
(iii) Lovastatin was discontinued, and his symptoms gradually resolved over seven days. 
 
Patient 2
(i) A 69-year-old woman was referred for medical attention for an evaluation of a cough.
(ii) She had been taking pravastatin, 20 mg to 40 mg daily, for 6 years.
(iii) She was given medication and her condition improved although tests revealed impaired lung function.
(iv) Over the next six weeks her symptoms became much worse and she was given medication.
(v) Despite the treatment her cough continued.
(vi) A scan found inflammation in the lungs.
(vii) A lung biopsy led to a diagnosis of pravastatin induced hypersensitivity pneumonitis. (Hypersensitivity pneumonitis is a disease in which your lungs become inflamed when they are exposed to substances to which you are allergic).
(viii) The pravastatin was stopped, and her cough resolved two weeks later.
(ix) A follow-up scan seven weeks after the first one showed complete resolution of the inflammation in her lungs.

Patient 3
(i) Three years after starting pravastatin 20 mg daily, a 77 year old man developed gradually increasing inflammation, with symptoms of polymyalgia. (Polymyalgia is pain, stiffness and tenderness in many muscles).
(ii) In addition, three years after starting pravastatin, the patient had retinal vein thrombosis. (Retinal vein thrombosis is when one of the tiny retinal veins becomes blocked by a blood clot).
(iii) The patient then developed a sudden worsening of his heart function.
(iv) After discontinuing the pravastatin his heart function normalized, and resolution of the polymyalgia syndrome occurred over one month.

Patient 4
(i) A 66-year-old man started taking lovastatin, 20 mg daily.
(ii) Four years later, the patient complained of fatigability, drowsiness, shortness of breath and joint pain.
(iii) Tests revealed inflammation and an autoimmune disorder.
(iv) He stopped taking lovastatin.
(v) His symptoms gradually resolved over two months.

Patient 5
(i) A 76-year-old woman  was started on lovastatin, 20 mg daily.
(ii) One year later she began to complain of muscle aches.
(iii) Two years later, she developed shortness of breath, joint pain and psoriasis. (Psoriasis is inflammation of the skin and develops as patches of red, scaly skin).
(iv) She then had a small heart attack and a failed artery graft.
(v) Lovastatin was discontinued, and she had a gradual improvement of her shortness of breath, joint pain, muscle pain and back pain over a two month period.

Patient 6
(i) An 80-year-old woman had been taking simvastatin, 10 mg daily, for 3 years.
(ii) She began having shortness of breath on exertion.
(iii) Investigations revealed she had inflammation.
(iv) Simvastatin was discontinued.
(v) Her shortness of breath improved and inflammation decreased over the next three weeks.

Patient 7
(i) A 49-year-old man had been taking pravastatin, 40 mg daily, for four years.
(ii) During this period, he had generalised itching and urticaria, along with swelling of his fingers and feet.
(iii) Test revealed an autoimmune disorder.
(iv) Pravastatin was discontinued, and the itching and swelling gradually resolved over the subsequent month.

Patient 8
(i) A 77-year-old woman was treated with pravastatin, 10 mg daily, for 3 years.
(ii) During this period, she had generalised itching with urticaria.
(iii) Investigations revealed she had inflammation and an autoimmune disorder.
(iv) Her symptoms cleared one month after discontinuing the pravastatin.

Patient 9
(i) A 53 year old man started to take pravastatin 40 mg daily.
(ii) Within six months he developed angioedema (swelling) of the eyelids and a sensation of his airway closing. 
(iii) He discontinued pravastatin.
(iv) His symptoms gradually resolved 30 days later.

Patient 10
(i) A 73-year-old man developed intense itching and urticaria after taking pravastatin 20 mg daily for three years. 
(ii) Tests revealed she had an autoimmune disorder.
(iii) He discontinued pravastatin and 12 days later his symptoms resolved.

Dr Liebhaber concluded: "We feel it is important for clinicians to recognize early symptoms of statin drug hypersensitivity because they are potentially life-threatening".

Statins cause a drop in energy levels and more fatigue

This paper was published in the Archives of Internal Medicine 2012 Aug 13:1-2

Study title and authors:

Effects of Statins on Energy and Fatigue With Exertion: Results From a Randomized Controlled Trial.

Golomb BA, Evans MA, Dimsdale JE, White HL.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/22688574

The study investigated the impact of statins on energy or exertional fatigue. The study lasted for six months and included 1,016 subjects, (692 men 20 years or older and 324 nonprocreative women), who were allocated to receive either 20-mg simvastatin, 40-mg pravastatin or placebo. The subjects rated their energy and fatigue with exertion levels at the start of the study and after six months.

The study found:

(a) Those taking statins had a significant drop in energy and more fatigue on exertion. Women were more affected than men especially those taking simvastatin.

(b) Four in ten women taking simvastatin cited worsening of energy or exertional fatigue compared to women taking placebo.

(c) Two in ten women taking simvastatin cited worsening of energy and exertional fatigue compared to women taking placebo.

(d) Two in ten women taking simvastatin rated themselves "much worse" energy or exertional fatigue compared to women taking placebo.

(e) One in ten women taking simvastatin rated themselves "much worse" energy and exertional fatigue compared to women taking placebo.

The results of the study show that statin usage leads to a drop in energy levels and a worsening of exertional fatigue.

Decrease of Coenzyme Q10 during treatment with statins

This post includes a summary of a paper published in Molecular Aspects of Medicine 1997;18 Suppl:S137-44

Books:

Study title and authors:

Dose-related decrease of serum coenzyme Q10 during treatment with HMG-CoA reductase inhibitors.

Mortensen SA, Leth A, Agner E, Rohde M.

Department of Medicine B, National University Hospital, Rigshospitalet, Copenhagen, Denmark.

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/9266515

Mortensen notes that coenzyme Q10 (ubiquinone) is an antioxidant, a molecule that is essential in the chemical reactions of the mitochondria (for energy production) and may help to prevent clogged arteries.

This randomised in a double-blind trial investigated the effect of statin drugs on coenzyme Q10 levels. The trial included 45 patients with "high" cholesterol who were treated with increasing dosages of either lovastatin (20-80 mg per day) or pravastatin (10-40 mg per day) over a period of 18 weeks.

The study found after 18 weeks of statin therapy:
(a) The coenzyme Q10 levels of patients taking lovastatin decreased by 29%.
(b) The coenzyme Q10 levels of patients taking pravastatin decreased by 20%.

Mortensen concludes that: "continued vigilance of a possible adverse consequence from coenzyme Q10 lowering seems important during long-term (statin) therapy".

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Statins, lack of energy and ubiquinone (Coenzyme Q10)

This post includes a summary of a study published in the British Journal of Clinical Pharmacology 2005 May; 59(5): 606–607

Books:

Study title and author:

Statins, lack of energy and ubiquinone

Marcus M Reidenberg

Weill Medical College of Cornell University, New York, NY 10021, USA

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1884835/

Reidenberg notes how the painful or tender muscle disease with elevated creatine phosphokinase levels due to statin drugs is well described. Statin muscle disease can also occur without elevated creatine phosphokinase levels or pain. More common is a feeling of lack of energy in people taking these drugs. Since statins block mevalonate synthesis, they lower levels of ubiquinone (coenzyme Q10), an essential compound for mitochondrial energy production. Thus, these people may truly lack energy.

Reidenberg reports:
(i) A randomized double-blind trial comparing 35 mg coenzyme Q10 with placebo bid was initiated for patients on statins who felt lack of pep or energy since starting the statins and who did not have muscle pain, tenderness, or elevated creatine phosphokinase.
(ii) By the time this trial started, most patients with these symptoms either stopped the statin or started coenzyme Q10 on their own, thus only three subjects were accrued in 1.5 years and the trial was stopped.
(iii) The three subjects ages were 68, 69, and 75. Their coenzyme Q10 levels prior to the coenzyme Q10 suplementation were 0.40, 0.35, and 0.36 µg ml⁻¹ (normal values are 0.69 - 1.06).
(iv) Two subjects received placebo and one received coenzyme Q10.
(v) After two weeks, subjects were asked how they felt. Both subjects taking placebo felt unchanged during the treatment period. The patient receiving coenzyme Q10 stated that several days after starting the study drug, she felt more energetic and could now walk 20 (short New York City) blocks instead of the two blocks that tired her before.
(vi)  One of the placebo patients was given coenzyme Q10 for an additional  two week period. After two weeks, he claimed that he had more energy climbing stairs and was less tired than before.
(vii) Statins lower levels of coenzyme Q10 and our subjects had levels below normal values.
(viii) Statins decrease mitochondrial activity.
(ix) Preliminary data suggests that coenzyme Q10 may reverse the age-related change in skeletal muscle fibre composition.

Reidenberg concludes: "Whether the level of fatigue and feeling of lack of energy in some people taking statins is related to skeletal muscle effects of these drugs is unknown. The results of this abbreviated randomized double-blind trial suggest it may be due to decreased ubiquinone (coenzyme Q10) levels due to effective statin inhibition of mevalonate synthesis. This would be an unintended adverse effect of the intended pharmacological action of the statin. People taking statins who describe lack of pep or energy may really lack energy because of a deficiency of ubiquinone (coenzyme Q10)".

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Statins reduce Coenzyme Q10 by 25%

This post includes a summary of a study published in the European Journal of Clinical Pharmacology 1994;46(4):313-7

Study title and authors:

Books:

Serum ubiquinone concentrations after short- and long-term treatment with HMG-CoA reductase inhibitors.

Laaksonen R, Ojala JP, Tikkanen MJ, Himberg JJ.
Department of Clinical Pharmacology, University of Helsinki, Finland.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/7957515

This study analysed the effect of long- and short-term statin treatment on the levels of ubiquinone (coenzyme Q10). The study included 17 men with "high" cholesterol who had their coenzyme Q10 levels were measured:
(i) After they had received simvastatin (20-40 mg per day) for 4.7 years.
(ii) After a 4 week treatment pause.
(iii) Again after they had resumed treatment with lovastatin (20-40 mg per day) for 12 weeks.

The study found:
(a) During the statin treatment pause the average coenzyme Q10 levels increased by 32%.
(b) Resumption of statin treatment caused a reduction of 25% in coenzyme Q10 levels.

Coenzyme Q10 is a nutrient that every cell in the body must have in order to produce energy. See here and here

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Statin side effects

This post includes a summary of a study published in Biofactors 2005;25(1-4):147-52

Study title and authors:
Treatment of statin adverse effects with supplemental Coenzyme Q10 and statin drug discontinuation.

Books:

Langsjoen PH, Langsjoen JO, Langsjoen AM, Lucas LA.

East Texas Medical Center and Trinity Mother Francis Hospital, Tyler, 75701, USA. langsjoen@compuserve.com

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/16873939

This study investigated the effects of discontinuing statin drugs and beginning Coenzyme Q10 supplementation in cardiology (heart disorder) clinic patients. The study included  The study included fifty new cardiology clinic patients who were on statin drug therapy (for an average of 28 months), who on their initial visit were evaluated for possible adverse statin effects (muscle pain, fatigue, shortness of breath, memory loss, and peripheral neuropathy). All patients discontinued statin therapy due to side effects and began supplemental Coenzyme Q10. The patients were followed for an average of 22 months.

The study found that after stopping statins and starting Coenzyme Q10:
(a) Fatigue decreased from 84% to 16%.
(b) Muscle pain decreased from 64% to 6%.
(c) Shortness of breath decreased 58% to 12%.
(d) Memory loss decreased from 8% to 4%.
(e) Peripheral neuropathy decreased from 10% to 2%.
(f) Measurements of heart function either improved or remained stable in the majority of patients.
(g) There was no adverse consequences from statin discontinuation.

The researchers conclude that: "Statin-related side effects, including statin cardiomyopathy, are far more common than previously published and are reversible with the combination of statin discontinuation and supplemental Coenzyme Q10".

*Dietary sources of Coenzyme Q10 include all animal products, particularly heart meat.

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