Hard scientific evidence of the effects of diet, pharmaceutical drugs & lifestyle on health from over 1,400 studies from research centers, universities and peer reviewed scientific journals.

My aim is to make this website the No: 1 worldwide go to place to access the actual scientific papers on the subjects of statins, cholesterol and saturated fat.

Research by David Evans

Tuesday, 31 March 2015

2015 Mar 23. pii: S0039-128X(15)00110-5. doi: 10.1016/j.steroids.2015.03.011. [Epub ahead of print]

Increased plant sterol deposition in vascular tissue characterizes patients with severe aortic stenosis and concomitant coronary artery disease.


The aim of the study was to evaluate the relationship between phytosterols, oxyphytosterols, and other markers of cholesterol metabolism and concomitant coronary artery disease (CAD) in patients with severe aortic stenosis who were scheduled for elective aortic valve replacement. Markers of cholesterol metabolism (plant sterols and cholestanol as markers of cholesterol absorption and lathosterol as an indicator of cholesterol synthesis) and oxyphytosterols were determined in plasma and aortic valve tissue from 104 consecutive patients with severe aortic stenosis (n=68 statin treatment; n=36 no statin treatment) using gas chromatography-flame ionization and mass spectrometry. The extent of CAD was determined by coronary angiography prior to aortic valve replacement. Patients treated with statins were characterized by lower plasma cholesterol, cholestanol, and lathosterol concentrations. However, statin treatment did not affect the sterol concentrations in cardiovascular tissue. The ratio of campesterol-to-cholesterol was increased by 0.46 ± 0.34 μg/mg (26.0%) in plasma of patients with CAD. The absolute values for the cholesterol absorption markers sitosterol and campesterol were increased by 18.18 ± 11.59 ng/mg (38.8%) and 11.40 ± 8.69 ng/mg (30.4%) in the tissues from patients with documented CAD compared to those without concomitant CAD. Campesterol oxides were increased by 0.06 ± 0.02 ng/mg (17.1%) in the aortic valve cusps and oxidized sitosterol-to-cholesterol ratios were up-regulated by 0.35 ± 0.2 ng/mg (22.7%) in the plasma of patients with CAD. Of note, neither cholestanol nor the ratio of cholestanol-to-cholesterol was associated with CAD. Patients with concomitant CAD are characterized by increased deposition of plant sterols, but not cholestanol in aortic valve tissue. Moreover, patients with concomitant CAD were characterized by increased oxyphytosterol concentrations in plasma and aortic valve cusps.

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/25814070
2015;2015:721078. Epub 2015 Feb 28.

Rhabdomyolysis Occurring under Statins after Intense Physical Activity in a Marathon Runner.

Toussirot É, Michel F2, Meneveau N3.


Statins are widely used in the treatment of hypercholesterolemia and their side effects on muscles are well established. Conversely, data are sparse regarding the safety of this class of drugs in subjects who engage in sports, particularly those who have intense sports activity. We report the case of a marathon runner who presented with acute rhabdomyolysis during competition while being under rosuvastatin treatment. This case raises the question of the need for temporary discontinuation of statin therapy when intense physical activity is planned.

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

1. Introduction Statins are widely prescribed for the primary or secondary prevention of cardiovascular events. It is estimated that approximately 25 million people around the world are receiving statin therapy [1]. In parallel, lifestyle counselling from our health systems is resulting in an ever-increasing number of people doing sport, sometimes at levels close to that of professional athletes. This is particularly true of running, which has become hugely popular in recent years, with more and more enthusiasts, especially competitors in long-distance races. These athletes who sometimes have dyslipidemia are usually treated. The safety of lipid-lowering drugs, especially statins, during intense physical activity in athletes is therefore increasingly topical. 2. Case Presentation A 50-year old man, without any noteworthy medical history, presented with hypercholesterolemia, without cardiovascular consequences. Due to a family history of myocardial infarction and a low-density lipoprotein (LDL) cholesterol level of 1.62 g/L, atorvastatin was prescribed at a dose of 10 mg/day in November 2011 but caused severe myalgia and was rapidly replaced by rosuvastatin at a dose of 5 mg/day. The patient suffered no muscle pain under rosuvastatin. The patient was a regular long-distance and marathon runner. He was preparing for an international competition under rosuvastatin treatment without any particular side effects. On the day of the competition in April 2012 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. The pains receded about 5 minutes after rest and rehydration. Muscle enzymes (creatine kinase, CK) were tested 2 days after the race and were at 2631 IU/L (normal levels < 300) (Table 1). There was no sign of renal insufficiency or modification of thyroid-stimulating hormone (TSH) or myoglobinuria. Hindawi Publishing Corporation Case Reports in Rheumatology Volume 2015, Article ID 721078, 2 pages http://dx.doi.org/10.1155/2015/721078 2 Case Reports in Rheumatology Table 1: Muscle enzyme (creatine kinase, CK) levels during training under rosuvastatin, during a marathon under rosuvastatin, and during a second marathon without rosuvastatin. CK measurement CK (UI/L) (normal < 300) Marathon under rosuvastatin therapy 2631 Usual training under rosuvastatin therapy 343 Marathon without rosuvastatin 650 The CK rate normalized after a few days of rest, and the rosuvastatin treatment was maintained. CK rates were tested again some time after the marathon while the patient was still under rosuvastatin and continuing normal training and were shown to be slightly elevated (Table 1). One year later, for another marathon, the patient temporarily discontinued the rosuvastatin therapy 3 months before the race. This time, the patient felt no muscle weakness at all or muscle contractions after the race. CK levels measured two days after the race were at 650 IU/L. 3. Discussion This subject presented with statin-induced muscle adverse event during competition. Rhabdomyolysis is usually defined as CK level more than 10 times the upper limit of normal. In our case, CK enzymes were available 2 days after the race, at levels that were near this definition, suggesting that the subject experienced rhabdomyolysis. In addition, he had had previously severe myalgia under low-dose atorvastatin (10 mg) without marathon running, suggesting that he was a statin-susceptible person. The adverse effects of statins on muscle performance are well established [1, 2]. The frequency of muscular effects under statin therapy is estimated to range between 5 and 20% in case series or observational studies and between 1.5 and 5% in randomized studies [1]. In the PRIMO observational study of 7924 dyslipidemic patients receiving a statin in France, the frequency of muscular symptoms was 10.5% [3]. The muscular effects of statins are variable and can manifest as an isolated elevation of CK levels without clinical symptoms or may be felt as myalgia, myositis or rhabdomyolysis, or immune-mediated necrotizing myopathy [1, 2]. All these side effects are a serious limitation to statin prescription. Factors that facilitate the occurrence of such symptoms have been identified, including advanced age, female sex, a low body mass index, hypothyroidism, renal or hepatic insufficiency, intercurrent infection, vitamin D deficiency, or physical activity. Atorvastatin is reportedly more frequently associated with these side effects, contrary to hydrophilic statins (rosuvastatin, pravastatin) [1].There is little data about the precipitating role of physical exercise in the development of muscle lesions in statin-taking subjects.The effect of statins on muscle strength and exercise performance was evaluated in a series of 420 healthy subjects who were taking either a statin or placebo. Muscle strength did not change under statin therapy, but a significant increase in muscle enzymes (CK) was observed with statin therapy versus placebo [4]. Another study reported muscle pain and hyperleukocytosis in a long-distance runner taking statins, with biological results linking the myalgia to muscle inflammation [5]. It has also been reported that competitive athletes poorly tolerate statins. In a series of 22 athletes with hypercholesterolemia, initiation of statin therapy was accompanied by onset of muscle pain in 78% of cases, regardless of the drug used or the sport [6]. Conversely, the intense physical activity associated with running a marathon (without statin therapy) can induce histological lesions corresponding to muscle fiber necrosis and inflammation [7]. Taken together, these data suggest that intense physical activity, as performed by statintreated athletes (whether professional or not and particularly during long-distance races) could have adverse consequences on muscles. Caution is therefore required when prescribing statins in this population, or in dyslipidemic patients who may change their lifestyle and take up intense physical exercise. In these circumstances and particularly in the case of competition requiring predictably intense exercise as in our case report, a prudent approach should be preferred, recommending temporary discontinuation of statin therapy, with reintroduction of therapy after the competition. Conflict of Interests The authors declare that there is no conflict of interests regarding the publication of this paper. References [1] S. Sathasivam, “Statin induced myotoxicity,” European Journal of Internal Medicine, vol. 23, no. 4, pp. 317–324, 2012. [2] M. Tomaszewski, K. M. Ste¸pien, J. Tomaszewska, and S. ´ J. Czuczwar, “Statin-induced myopathies,” Pharmacological Reports, vol. 63, no. 4, pp. 859–866, 2011. [3] E. Bruckert, G. Hayem, S. Dejager, C. Yau, and B. Begaud, ´ “Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients—the PRIMO study,” Cardiovascular Drugs and Therapy, vol. 19, no. 6, pp. 403–414, 2005. [4] B. A. Parker, J. A. Capizzi, A. S. Grimaldi et al., “Effect of statins on skeletal muscle function,” Circulation, vol. 127, no. 1, pp. 96– 103, 2013. [5] S. J. Semple, “Statin therapy, myopathy and exercise—a case report,” Lipids in Health and Disease, vol. 11, article 40, 2012. [6] H. Sinzinger and J. O’Grady, “Professional athletes suffering from familial hypercholesterolaemia rarely tolerate statin treatment because of muscular problems,” British Journal of Clinical Pharmacology, vol. 57, no. 4, pp. 525–528, 2004. [7] R. S. Hikida, R. S. Staron, F. C. Hagerman, W. M. Sherman, and D. L. Costill, “Muscle fiber necrosis associated with human marathon runners,” Journal of the Neurological Sciences, vol. 59, pp. 185–203, 1983.


Sunday, 29 March 2015

Acute exacerbations and infections increase in patients with chronic obstructive pulmonary disease who take aspirin and statins

This study was published in the International Journal of Medical Sciences 2015 Mar 2;12(3):280-7
Study title and author:
No Significant Detectable Anti-infection Effects of Aspirin and Statins in Chronic Obstructive Pulmonary Disease.
Yayan J.
Department of Internal Medicine, Division of Pulmonary, Allergy and Sleep Medicine, Saarland University Medical Center, Homburg/Saar, Germany.
This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/25798054

Chronic obstructive pulmonary disease is the name for a collection of lung diseases including chronic bronchitis, emphysema and chronic obstructive airways disease.

This study examined  the effect of using aspirin and statins in the exacerbation and infection in patients with chronic obstructive pulmonary disease. The study included 300 patients, average age 69 years, with chronic obstructive pulmonary disease.

The study found:
(a) Patients taking aspirin and statins were 40% more likely to develop an infection than not develop an infection.
(b) Patients taking statins alone were 230% more likely to develop an infection than not develop an infection.
(c) Patients not taking either aspirin or statins were 40% LESS likely to develop an infection than develop an infection.
(d) Patients taking aspirin and statins had a 16% increased risk of acute exacerbation of chronic obstructive pulmonary disease compared to patients not taking either aspirin or statins.
(e) Patients taking statins alone had a 56% increased risk of acute exacerbation of chronic obstructive pulmonary disease compared to patients not taking either aspirin or statins.

Yayan concluded: "In this study, the number of acute exacerbations and infections increased in patients with chronic obstructive pulmonary disease who took aspirin and statins compared with those who took neither aspirin nor statins".

Thursday, 26 March 2015

Women who consume diet drinks have a higher risk of cardiovascular disease

This study was published in the Journal of General Internal Medicine 2014 Dec 17

Study title and authors:
Diet Drink Consumption and the Risk of Cardiovascular Events: A Report from the Women's Health Initiative.
Vyas A, Rubenstein L, Robinson J, Seguin RA, Vitolins MZ, Kazlauskaite R, Shikany JM, Johnson KC, Snetselaar L, Wallace R.
Division of Cardiovascular Medicine, University of Iowa Hospitals & Clinics, 200 Hawkins Dr., Int. Med. E316-1 GH, Iowa City, IA, 52242, USA, ankurvyas7@gmail.com.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/25515135

This study aimed to evaluate the relationship between diet drink intake and cardiovascular events. The study included 59,614 post-menopausal women, average age 62.8 years, who were followed for 8.7 years.

The study found:
(a) Women who consumed two or more diet drinks per day had a 30% higher risk of cardiovascular disease events compared to women who consumed 0-3 diet drinks a month.
(b) Women who consumed two or more diet drinks per day had a 50% higher risk of cardiovascular disease deaths compared to women who consumed 0-3 diet drinks a month. 
(c) Women who consumed two or more diet drinks per day had a 30% higher risk of overall deaths compared to women who consumed 0-3 diet drinks a month.

Vyas concluded: "This analysis demonstrates an association between high diet drink intake and cardiovascular disease outcomes and mortality in post-menopausal women".

Monday, 23 March 2015

Statins may increase the risk of liver disease in patients with Graves orbitopathy

This study was published in the Journal of Clinical Endocrinology and Metabolism 2015 Mar 9

Study title and authors:
Covelli D, Vannucchi G, Campi I, Currò N, D'Ambrosio R, Maggioni M, Gianelli U, Beck-Peccoz P, Salvi M.

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/25751109

Graves' orbitopathy is an autoimmune inflammatory disorder affecting the orbit around the eye, characterized by upper eyelid retraction, lid lag, swelling, redness, conjunctivitis, and bulging eyes.

Graves' orbitopathy is often treated with methylprednisolone (an intravenous glucocorticoid). Often patients with Graves' orbitopathy and using an intravenous glucocorticoid, are also treated with statins.

This paper records the cases of two patients, (a 64 years old man and a 58 years old woman), who were prescribed methylprednisolone and concomitant administration of statins.

In the 64 year old man:
(a) After starting simvastatin and methylprednisolone he suffered from liver dysfunction. (His liver enzymes were significantly increased).
(b) He stopped taking simvastatin and methylprednisolone.
(c) He restarted methylprednisolone (but not simvastatin) and his liver enzymes returned to normal.

In the 58 year old woman:
(d) After starting rosuvastatin and methylprednisolone she suffered from liver dysfunction. (Her liver enzymes were significantly increased).
(e) She stopped taking methylprednisolone but continued rosuvastatin.
(f) Her live enzymes increased further.
(g) Three weeks later she stopped the rosuvastatin and there was a progressive normalization of her liver enzymes.

Covelli concluded: "Our study shows that statins, when concomitantly employed with methylprednisolone, may be a cause of liver dysfunction during intravenous glucocorticoid in active Graves' orbitopathy".

Thursday, 19 March 2015

Statins and low cholesterol associated with a higher risk of Parkinson's disease

This study was published in Movement Disorders 2015 Jan 14

Study title and authors:
Statins, plasma cholesterol, and risk of Parkinson's disease: A prospective study.
Huang X, Alonso A, Guo X, Umbach DM, Lichtenstein ML, Ballantyne CM, Mailman RB, Mosley TH, Chen H.
Department of Neurology, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/25639598

This study examined the relationship between cholesterol levels and statin use in relation to Parkinson's disease. The study included 15,792 participants, aged 45-64 years, who were followed for 11 years.

The study found:
(a) Statin users had a 139% higher risk of Parkinson's compared to non-users.
(b) Those with the highest cholesterol had a 57% reduced risk of Parkinson's compared to those with the lowest cholesterol.

Professor Huang concluded: "Statin use may be associated with a higher Parkinson's disease risk, whereas higher total cholesterol may be associated with lower risk".

Sunday, 15 March 2015

Statins associated with elevated risk of high-grade prostate cancer

This study was published in the European Journal of Cancer 2015 Feb 23. pii: S0959-8049(15)00124-0
Study title and authors:
The risk of prostate cancer for men on aspirin, statin or antidiabetic medications.
Nordström T, Clements M, Karlsson R, Adolfsson J, Grönberg H.
This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/25727881

This study estimated the association between prescribed medications and the risk of either any prostate cancer or high-grade prostate cancer. The study included 185,667 men having a first recorded prostate specific antigen test and 18,574 men having a first prostate biopsy.

Regarding statins, the study found:
(a) Men using statins had a 16% increased risk of any prostate cancer compared to men not taking statins.
(b) Men using statins had a 25% increased risk of high-grade prostate cancer compared to men not taking statins. 

Nordstrom concluded: "Use of any statins was associated with an elevated risk of being diagnosed with high-grade prostate cancer".