The raison d'etre of this website is to provide you with hard scientific information which may help you make informed decisions in your quest for health (so far I have blogged concise summaries of over 1,500 scientific studies and have had three books published).

My research is mainly focused on the effects of cholesterol, saturated fat and statin drugs on health. If you know anyone who is worried about their cholesterol levels and heart disease, or has been told to take statin drugs you could send them a link to this website, and to my statin or cholesterol or heart disease books.

David Evans

Independent Health Researcher

Sunday, 1 May 2016

Statin treatment associated with depleted levels of coenzyme Q10 and cytochrome oxidase

This study was published in Toxicology Mechanisms and Methods 2009 Jan;19(1):44-50
 
Study title and authors:
Decreased ubiquinone availability and impaired mitochondrial cytochrome oxidase activity associated with statin treatment.
Duncan AJ, Hargreaves IP, Damian MS, Land JM, Heales SJ.
Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 1BG, UK.
 
This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/19778232

This study investigated the involvement of statins in impaired cellular energy production. Mitochondria are the cells power plants, and coenzyme Q10 (ubiquinone) and cytochrome oxidase (complex IV) are vital enzymes needed in cellular energy production.

In a study published in the Journal of the American College of Cardiology, coenzyme Q10 (ubiquinone) was shown to lower cardiovascular deaths by 43% and lower the overall death rate by 42%.

Cytochrome oxidase (Complex 4) deficiency is a condition that can affect several parts of the body, including the muscles used for movement (skeletal muscles), the heart, the brain, or the liver. Cytochrome oxidase deficiency can lead to muscle weakness (myopathy), poor muscle tone (hypotonia), severe brain dysfunction (encephalomyopathy). Approximately one quarter of individuals with cytochrome oxidase deficiency have a type of heart disease that enlarges and weakens the heart muscle (hypertrophic cardiomyopathy). Another possible feature of this condition is an enlarged liver, which may lead to liver failure. Most individuals with cytochrome c oxidase deficiency have a buildup of a chemical called lactic acid in the body (lactic acidosis), which can cause nausea and an irregular heart rate, and can be life-threatening. Many people with cytochrome oxidase deficiency have a loss of mental function, movement problems, hypertrophic cardiomyopathy, eating difficulties, and brain abnormalities. Cytochrome oxidase deficiency is frequently fatal in childhood.

(i) Two patients experiencing muscle problems following treatment with simvastatin (40 mg per day) and cyclosporin (patient 1) and simvastatin (40 mg per day) and itraconazole (patient 2).
(ii) Analysis of the two patients skeletal muscle revealed a decreased ubiquinone status (77 and 132; reference range: 140-580 pmol/mg) and decreased complex IV activity (0.006 and 0.007 reference range: 0.014-0.034).
(iii) To assess statin treatment in the absence of possible pharmacological interference from cyclosporin or itraconazole, primary astrocytes (cells from the central nervous system) were cultured with lovastatin.
(iv) Lovastatin treatment resulted in a decrease in ubiquinone (statin treatment 97.9 versus control 202.9 pmol/mg), and a decrease in complex IV activity (statin treatment 0.008 versus control: 0.011).

Duncan concludes: "These data, coupled with the patient findings, indicate a possible association between statin treatment, decreased ubiquinone status, and loss of complex IV activity".

Sunday, 24 April 2016

List of some drugs that may cause side effects when coadministered with statins

This paper was published in the Medical Journal of Australia 2001 Nov 5;175(9):486-9

Study title and author:
Statin-associated myopathy.
Hamilton-Craig I.
North Adelaide Cardiac Clinic, SA. admin@medped-aust.com

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/11758079

Dr Hamilton-Craig notes that myopathy (muscle disease) can be caused by all statins.

In this review he finds:
(a)  The risk of myopathy is increased by: the use of high doses of statins, concurrent use of fibrates, concurrent use of hepatic cytochrome P450 inhibitors, acute viral infections, major trauma, surgery, hypothyroidism and other conditions.
(b) Cytochrome P450 are enzymes that give protection against potential toxicity from the foods and drugs (including statins) that we ingest by breaking down and eliminating the toxic substance. These enzymes are found primarily within liver cells as well as many other cell types. Cytochrome P450 inhibitors inhibit the effectiveness of cytochrome P450 enzymes and thereby increase the levels of statins in the body which leads to increased toxicity and more side effects. Cytochrome P450 inhibitors include: Amiodarone; (Cordarone), Azole Antifungals; Fluconazole (Diflucan), Itraconazole (Sporanox), Ketoconazole (Nizoral), Posaconazole (Noxafil, Posanol), Voriconazole (Vfend), Calcium Channel Blockers; (Amlodipine, Diltiazem, Verapamil), Cyclosporine; (Neoral), Danazol; (Cyclomen), Dronedarone (Multaq), Fibric Acid Derivatives; (Fenofibrate, Gemfibrozil), Glyburide; Grapefruit/Grapefruit Juice; Macrolide Antibiotics; Clarithromycin (Biaxin), Erythromycin, Nefazodone; Phenytoin; (Dilantin), Protease Inhibitors; Atazanavir (Reyataz), Boceprevir (Victrelis), Darunavir (Prezista), Fosamprenavir (Lexiva, Telzir), Indinavir (Crixivan), Lopinavir/Ritonavir (Kaletra), Nelfinavir (Viracept), Ritonavir (Norvir), Saquinavir (Invirase), Telaprevir (Incivek), Tipranavir (Aptivus), Ranolazine (Ranexa), Telithromycin (Ketek),
Ticagrelor (Brilinta).
(c) Statin-associated myopathy should be suspected when a statin-treated patient complains of unexplained muscle pain, tenderness or weakness.
(d) Statin therapy should be stopped in cases of suspected myopathy.

Sunday, 17 April 2016

"Recovered" unpublished data reveals that lowering cholesterol levels increase the risk of death by 22%

This study was published in the BMJ 2016 Apr 12;353:i1246

Study title and authors:
Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73).
Ramsden CE, Zamora D, Majchrzak-Hong S, Faurot KR, Broste SK, Frantz RP, Davis JM, Ringel A, Suchindran CM, Hibbeln JR.
USA Department of Physical Medicine and Rehabilitation, Program on Integrative Medicine, University of North Carolina, Chapel Hill, NC, USA Chris.Ramsden@nih.gov.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/27071971

The objective of this study was to review the findings (by analysing unpublished "recovered" data from the original study investigators) of the Minnesota Coronary Experiment. The Minnesota Coronary Experiment was a double blinded, parallel group, randomized controlled dietary intervention trial conducted between 1968 - 1973, and was to designed to prove that increasing the polyunsaturated fat, (linoleic acid), and decreasing saturated fat in the diet would reduce cardiovascular events and deaths. It was the largest (9,570 participants, aged 20-97 years) and perhaps the most rigorously executed dietary trial of cholesterol lowering by replacement of saturated fat with vegetable oil rich in linoleic acid.

In the study participants were recruited from mental hospitals or nursing homes in the Minnesota area. They were divided into two groups:
(1) The intervention diet group had their dietary saturated fat cut in half (from 18.5% to 9.2% of calories) and their polyunsaturated linoleic fat intake massively increased from 3.4% to 13.2% of calories (a 280% increase).
(2) The control diet group did not change their saturated fat intake but did increase polyunsaturated linoleic acid intake from 3.4% to 4.7% of calories.

The "recovered" data, included previously unpublished records of serum cholesterol and autopsy reports and an extensive collection of study documents.

Using the "recovered" data the study found:
(i) The intervention group had significant reduction in cholesterol levels of 13.8%.
(ii) The control group had a small reduction in cholesterol levels of 1%.
(iii) A 30 mg/dL (0.78 mmol/L) decrease in cholesterol levels was associated with 22% higher risk of death from any cause.
(iv) Autopsy reports showed that participants in the intervention diet group had a 90% increased risk of a heart attack compared to participants in the control diet group. 

The researchers also did a systematic review of the scientific literature and identified five randomized controlled trials that provided vegetable oil(s) rich in linoleic acid in place of saturated fat. These five trials included 10,808 participants. The average change in cholesterol levels in the course of the randomized controlled trials ranged from 7.8% to 13.8% lower in the intervention versus control groups.

The review of the five trials found:
(v) Those in the (low cholesterol) intervention groups had a 13% increased risk of death from coronary heart disease compared to those in the higher cholesterol control groups.
(vi) Those in the (low cholesterol) intervention groups had a 7% increased risk of death from all causes compared to those in the higher cholesterol control groups. 

The above investigators also "recovered" unpublished data from the Sydney Diet Heart Study (1966-73) where the results of the trial was not fully reported. Ramsden commented: "Our recovery and 2013 publication of previously unpublished data from the Sydney Diet Heart Study (SDHS, 1966-73) belatedly showed that replacement of saturated fat with vegetable oil rich in linoleic acid significantly increased the risks of death from coronary heart disease and all causes, despite lowering serum cholesterol."

Critical points arise from this study:
(1) Key findings from landmark randomized controlled trials including the Sydney Diet Heart Study and the Minnesota Coronary Experiment were not fully published.
(2) Participants who had greater reductions in cholesterol levels had a higher, rather than lower, risk of death.

The question must be asked: "Why did the original investigators suppress this information?"

Is it because the results of the studies were clearly at odds with their beliefs?

Ramsden concluded: "It is interesting to speculate whether complete publication of randomized controlled trial results might have altered key policy decisions promoting replacement of saturated fat with linoleic acid rich oils (such as the 1977 McGovern report and National Cholesterol Education Program (1984-85) or contributed to a shift in research priorities."
  

Wednesday, 13 April 2016

Healthy old people have high cholesterol

This study was published in the Japanese Journal of Clinical Medicine 2009 Jul;67(7):1343-7

Study title and authors:
Clues to the exceptional longevity --morbiditiy and functional status of Tokyo-area centenarians
Takayama M, Hirose N
Division of Geriatric Medicine, Department of Internal Medicine, Keio University School of Medicine.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/19591283

This study examined the association between various factors and physical & cognitive function in 302 people over a 100 years of age.

Regarding blood pressure and cholesterol levels, Takayama found that higher blood pressure, higher total cholesterol levels and higher high-density lipoprotein cholesterol levels were associated with better physical and cognitive function.

Takayama concluded: "This phenomenon might be one of the "centenarian paradox".

Dr Malcolm Kendrick will have a wry smile at yet another "health paradox." 

Saturday, 9 April 2016

Low cholesterol levels associated with a 528% increased risk of gastric cancer

This study was published in Scientific Reports 2016 Jan 28;6:19930

Study title and authors:
Apolipoprotein E epsilon 2 allele and low serum cholesterol as risk factors for gastric cancer in a Chinese Han population.
Kang R, Li P, Wang T, Li X, Wei Z, Zhang Z, Zhong L, Cao L, Heckman MG, Zhang YW, Xu H, Huang C, Bu G, Chen XF.
Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Medical College, Xiamen University, Xiamen 361102, China.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/26817942

One of the aims of this study was to evaluate the association between cholesterol levels and gastric cancer. The study included 550 gastric cancer patients and 550 cancer free control individuals.

Regarding cholesterol levels, the study found:
(a) Those with the lowest cholesterol levels (less than 4.29 mmol/L (165 mg/dL)) had a 528% increased risk of gastric cancer compared to those with the highest cholesterol levels (more than 5.75 mmol/L (222 mg/dL).
(b) Those with the lowest HDL cholesterol levels (less than 1.08 mmol/L (41 mg/dL)) had a 499% increased risk of gastric cancer compared to those with the highest HDL cholesterol levels (more than 1.63 mmol/L (63 mg/dL).
(c) Those with the lowest LDL cholesterol levels (less than 2.71 mmol/L (104 mg/dL)) had a 54% increased risk of gastric cancer compared to those with the highest LDL cholesterol levels (more than 3.97 mmol/L (153 mg/dL).

Kang concluded: "In summary, our study confirmed the associations of lower levels of serum cholesterol with the incidence of gastric cancer."

Links to other studies:
High cholesterol levels reduce the risk of stomach cancer
Low cholesterol is an independent risk factor for developing gastric cancer
Low HDL cholesterol levels increase the risk of gastric cancer

Monday, 4 April 2016

Pleurisy induced by atorvastatin

This study was published in Revue des Maladies Respiratories 2016 Mar 15. pii: S0761-8425(16)00054-1

Study title and authors:
Pleurisy induced by atorvastatin
Mansour Y, Masson P, Gourdier AL, Gagnadoux F, Trzepizur W.
D├ępartement de pneumologie, centre hospitalier universitaire d'Angers, 4, rue Larrey, 49033 Angers cedex 9, France.

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/26992330

Pleurisy is an inflammation of the pleura, which is the moist, double-layered membrane that surrounds the lungs and lines the rib cage. The condition can make breathing extremely painful. Sometimes it is associated with another condition called pleural effusion, in which excess fluid fills the area between the membrane's layers.

This paper reported the case of a man who developed pleural effusions after taking atorvastatin.
(i) An 84-year-old man sought medical attention for pleural effusions around both lungs.
(ii) He had started to take atorvastatin two years previously.
(iii) Investigations found no other cause could be found for the pleural effusions.
(iv) He stopped taking the statin and all his symptoms rapidly disappeared.
(v) He accidentally started to take atorvastatin again which resulted in recurrence of his symptoms, reinforcing the hypothesis that atorvastatin was responsible for this pleural effusion.

Links to other studies:
Statins induce pneumonia
Link between statin use and interstitial lung disease
Doctor says statin drug hypersensitivity reactions are potentially life-threatening

Tuesday, 29 March 2016

Statin use associated with a 27% increased risk of diabetes in heart attack and angina patients

This study was published in the Canadian Journal of Diabetes 2016 Mar 15. pii: S1499-2671(15)30026-5

Study title and authors:
Statin Use and the Risk for Incident Diabetes Mellitus in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention: A Population-Based Retrospective Cohort Study in Taiwan.
Lin ZF, Wang CY, Shen LJ, Hsiao FY, Lin Wu FL.
School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan;

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/26992286

Acute coronary syndrome is a term given to various heart conditions, including a heart attack and unstable angina. These conditions are due to there being a reduced amount of blood flowing to a part of the heart.

Percutaneous coronary intervention, or coronary angioplasty is a procedure to unblock a coronary artery.

The purpose of the study was to examine the association between statin use and the risk for diabetes in patients with acute coronary syndrome following percutaneous coronary intervention. The study include 9,043 statin users and 9,043 non-statin users.

The study found:
(a) Statin use was associated with a significant increase of 27% in the risk for new-onset diabetes compared to non-statin use.
(b) Almost all types of statins were associated with a statistically significant increase in the risk for new-onset diabetes compared to those without statin use.

Lin concluded: "Our study indicated an association between increased risk for new-onset diabetes mellitus and statin use."

Links to other studies: 
Atorvastatin associated with an increased death rate in diabetic patients
Statins increase the risk of diabetes by 48%
Statin use is associated with accelerated artery calcification in type two diabetes