Professor says it's a serious concern that statins make people less likely to exercise

This study was published in the Journal of the American Medical Association Internal Medicine 2014 Jun 9

Study title and authors:
Statins and Physical Activity in Older Men: The Osteoporotic Fractures in Men Study.

Lee DS, Markwardt S, Goeres L, Lee CG, Eckstrom E, Williams C, Fu R, Orwoll E, Cawthon PM, Stefanick ML, Mackey D, Bauer DC, Nielson CM.
Department of Pharmacy Practice, Oregon State University/Oregon Health and Science University College of Pharmacy, Portland.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/24911216

The objective of the study was to determine the effects of statins on physical activity. The study lasted for nine years and included 4,137 men (989 men (24%) were statin users and 3148 (76%) were nonusers) aged 65 years and older. The Physical Activity Scale for the Elderly (PASE) was used to measure physical activity. (A higher PASE score indicates a higher level of activity).

The study found:
(a) At the start of the study statin users had a 5.8 points lower PASE score than non users.
(b) PASE score declined by 2.5 points per year for non users.
(c) PASE score declined by 2.8 points per year for prevalent users of statins.
(d) PASE score declined by 3.4 points per year for new users of statins.
(e) Statin users engaged in 5.4 fewer minutes in moderate physical activity per day than non users.
(f) Statin users engaged in 0.6 fewer minutes in vigorous physical activity per day than non users.
(g) Statin users engaged in 7.6 more minutes in sedentary behaviour per day than non users.

Lead author of the study, David Lee, an assistant professor in the Orgeon State University and the Oregon Health and Science College of Pharmacy, said: "Physical activity in older adults helps to maintain a proper weight, prevent cardiovascular disease and helps to maintain physical strength and function. We're trying to find ways to get older adults to exercise more, not less. It's a fairly serious concern if use of statins is doing something that makes people less likely to exercise".

Links to other studies:
Statins block the ability of exercise to improve fitness levels
Statins, fibrates and beta blockers increase fatigue during moderate intensity exercise
Rhabdomyolysis occurring under statins after intense physical activity in a marathon runner



Rhabdomyolysis occurring under statins after intense physical activity in a marathon runner

This paper was published in Case Reports in Rheumatology 2015;2015:721078

Study title and authors:
Rhabdomyolysis Occurring under Statins after Intense Physical Activity in a Marathon Runner.

Toussirot É, Michel F, Meneveau N.
Clinical Investigation Center for Biotherapy, CIC-1431, FHU INCREASE, University Hospital of Besançon, 25000 Besançon, France

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/25815236

This paper reports the case of a marathon runner who developed rhabdomyolysis.

(i) A 50 year old man healthy man started to take atorvastatin but soon suffered from severe muscle pain. He then was prescribed rosuvastatin.
(ii) The patient was a regular long-distance and marathon runner. He was preparing for an international competition.
(iii) On the day of the competition and while being still under rosuvastatin, the patient experienced progressively worsening muscular weakness. At the end of the race, he suffered from severe pains in the lower limbs similar to diffuse cramps associated with generalized muscle contraction.
(iv) Muscle enzymes (creatine kinase) were tested two days after the race and were at 2631 IU/L (normal levels 300) and he was diagnosed with rhabdomyolysis.
(v) One year later, (without taking the statins), for another marathon, the patient felt no muscle weakness at all or muscle contractions after the race.

Toussirot concluded: "Intense physical activity, as performed by statin treated athletes (whether professional or not and particularly during long-distance races) could have adverse consequences on muscles".

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.

Statins block the ability of exercise to improve fitness levels

This study was published in the Journal of the American College of Cardiology 2013 Apr 10. pii: S0735-1097(13)01403-4

 

Study title and authors:

Simvastatin impairs exercise training adaptations.

Mikus CR, Boyle LJ, Borengasser SJ, Oberlin DJ, Naples SP, Fletcher J, Meers GM, Ruebel M, Laughlin MH, Dellsperger KC, Fadel PJ, Thyfault JP.

 

Division of Cardiology at Duke University Medical Center, Durham, NC.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/23583255

This study sought to determine if simvastatin hindered the positive effects of exercise for obese and overweight adults. The study, which lasted for 12 weeks, included 37 sedentary overweight or obese adults (aged 25-59) with at least two metabolic syndrome risk factors, who completed either:
(i) 12 weeks of aerobic exercise training.
(ii) 12 weeks of aerobic exercise training in combination with simvastatin (40 mg per day).

The study found:
(a) Cardiorespiratory fitness increased by 10% in response to exercise training alone, but was blunted by the addition of simvastatin resulting in only a 1.5% increase.
(b) Skeletal muscle mitochondrial content (the cells' energy production sites) increased by 13% in the exercise only group (a normal response following exercise training) but decreased by 4.5% in the simvastatin plus exercise group.

One of the study authors, John Thyfault, an associate professor of nutrition and exercise physiology at the University of Missouri School of Medicine, concluded: “Daily physical activity is needed to maintain or improve fitness, and thus improve health outcomes. However, if patients start exercising and taking statins at the same time, it seems that statins block the ability of exercise to improve their fitness levels.”

Statins exacerbate exercise-induced skeletal muscle injury

This study was published in Metabolism 1997 Oct;46(10):1206-10

 

Study title and authors:

Lovastatin increases exercise-induced skeletal muscle injury.

Thompson PD, Zmuda JM, Domalik LJ, Zimet RJ, Staggers J, Guyton JR.

Division of Cardiology, University of Pittsburgh, PA, USA.

 

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/9322808

This study investigated the association between statins, exercise and creatine kinase levels (high levels of creatine kinase are a marker for muscle damage) using a double-blind, placebo-controlled design. The study include 59 healthy men aged 18 to 65 years who were assigned to receive lovastatin (40 mg per day) or placebo for 5 weeks. The men completed 45 minutes of treadmill walking after 4 weeks of treatment.

The study found that the creatine kinase levels of the men who received lovastatin were 62% and 77% higher 24 and 48 hours after the treadmill exercise compared to the men who received placebo.

The researchers concluded that statins exacerbate exercise-induced skeletal muscle injury.

Statins impair energy production and promote muscle damage

This study was published in Muscle and Nerve 2011 Jan;43(1):76-81

Study title and authors:
Evaluation of skeletal muscle during calf exercise by 31-phosphorus magnetic resonance spectroscopy in patients on statin medications.

Wu JS, Buettner C, Smithline H, Ngo LH, Greenman RL.
Department of Radiology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, Massachusetts 02215, USA. jswu@bidmc.harvard.edu

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/21171098

Phosphocreatine is a substance that is fundamental to the ability of the body to produce muscular energy.

Elevated blood levels of creatine kinase are indicative of muscle damage.

The study investigated the association of statin treatment on recovery from exercise. The study included ten patients, (who were subject to a four-week regimen of statin therapy), who had their phosphocreatine and creatine kinase levels measured pre- and post-statin therapy.

The study found:
(a) Phosphocreatine levels took 97% longer to recover from exercise after statin therapy.
(b) Creatine kinase levels rose by 17.7% after statin therapy.

The results of the study suggest that statin therapy may impair energy production and promote muscle damage.

Do statins cause a deterioration in pain-free walking?

This post includes a synopsis of a study published in Vasa 2009 May;38(2):155-9

Study title and authors:
The influence of atorvastatin on walking performance in peripheral arterial disease.
Bregar U, Poredos P, Sabovic M, Jug B, Sebestjen M.
Department of Vascular Disease, University of Ljubljana Medical Centre, Ljubljana, Slovenia.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/19588303

Books:

The study investigated if statins could improve walking performance in patients with peripheral arterial disease. The patients were divided into 2 groups, the statin group (atorvastatin 20 mg/day), and the control group (placebo), and were asked to practice interval exercise for at least half an hour per day unto a maximum of one hour per day.

The study also measured the Ankle Brachial Pressure Index. The Ankle Brachial Pressure Index (ABPI), known more commonly as an ABI, is the ratio of the blood pressure in the lower legs to the blood pressure in the arms. Compared to the arm, lower blood pressure in the leg is an indication of blocked arteries (peripheral vascular disease). The ABI is calculated by dividing the systolic blood pressure at the ankle by the systolic blood pressures in the arm.

The study found:
(a) The ankle-brachial pressure index (ABPI) did not change significantly in either group.
(b) After 3 months the pain-free walking distance increased 41% in the statin group.
(c) After 3 months the pain-free walking distance increased 100% in the placebo group.

To conclude:
(i) Statins did not improve peripheral arterial disease (no change in the ankle-brachial pressure index).
(ii) The placebo group increased their pain-free walking distance by an extra 59% compared to the statin users. It may be argued that statins inhibited the expected progress of pain-free walking distance that 3 months of regular exercise shoud induce.

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Even brief exposure to statins causes muscle damage

This post includes a synopsis of a study published in the Archives of Neurology 2004 Jun;61(6):889-92

Study title and authors:
Atorvastatin decreases the coenzyme Q10 level in the blood of patients at risk for cardiovascular disease and stroke.
Rundek T, Naini A, Sacco R, Coates K, DiMauro S.
Department of Neurology, Columbia University College of Physicians & Surgeons, New York, NY 10032, USA.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/15210526

Books:

Rundek notes there have been various adverse effects of statin drugs, including problems commonly affecting muscle and ranging from muscle pain to the rapid destruction of skeletal muscle which can then cause kidney failure (rhabdomyolysis). These adverse effects may be due to a coenzyme Q(10) (CoQ(10)) deficiency because inhibition of cholesterol biosynthesis also inhibits the synthesis of CoQ(10).

The objective of the study was to measure CoQ(10) levels in blood from subjects with high cholesterol levels before and after exposure to atorvastatin at 14 and 30 days.

 
The study found:
(a) Coenzyme Q(10) levels dropped by 51% after 30 days of statin thearpy.
(b) A significant decrease was already detectable after 14 days of treatment.
 
To conclude: Even brief exposure to statins causes a marked decrease in blood CoQ(10) concentration. Widespread inhibition of CoQ(10) synthesis could explain the most commonly reported adverse effects of statins, especially exercise intolerance, muscle pain, and rhabdomyolysis.

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