New Cholesterol Drug PCSK9 is Likely to Prematurely Kill You.

Story at-a-glance

  • A new class of drugs known as PCSK9 inhibitors promises to reduce LDL cholesterol levels to previously unheard of lows, dropping your level below 50. These drugs will undoubtedly kill many before the risks are fully realized
  • Your body needs cholesterol for the production of cell membranes, hormones, vitamin D, and bile acids that help you to digest fat
  • If your levels get too low, you increase your risk of dementia, violent and aggressive behavior, depression, suicide, cancer, Parkinson’s disease—and likely heart disease, as a result of cholesterol sulfate deficiency
  • Statin drugs, which one in four adults over 45 are using to protect their heart health, can paradoxically have significantly detrimental effects on your heart health
  • The most effective way to optimize your cholesterol profile and prevent heart disease is via diet and exercise.
  • cholesterol (1)

In 2004, the US government’s National Cholesterol Education Program panel advised those at risk for heart disease to attempt to reduce their LDL cholesterolto less than 100, or even less than 70, if you’re very high risk. Prior to this, a 130-milligram LDL cholesterol level was considered healthy.

In order to obtain the incredibly low LDL levels now recommended, you typicallyhave to take a cholesterol-lowering statin drug, and sometimes two or three of them in combination.

Now, a new class of cholesterol drugs known as PCSK9 inhibitors promises to reduce LDL cholesterol levels to previously unheard of lows. Indeed, this type of drug can drop your level below 50!

My prediction? These drugs will absolutely kill people—not just some, but MANY. I cannot warn you against this terrible idea enough. While many worry that their cholesterol is too high, few give any thought at all to the damage that can result if your cholesterol is too low.

This is a topic near and dear to my heart, as I drove (without drugs) my own total cholesterol levels down to a risky 75 when I was a naive young doctor. Alas, when it comes to cholesterol, lower is not always better. In fact, when your cholesterol levels go too low, a host of negative things happen in your body.

Unfortunately, lowering cholesterol levels has become so common in the US that nearly every American reading this either knows someone struggling to do so, or has struggled to do so themselves.

This despite the fact that there is no evidence to support the notion that having an extremely low cholesterol level is beneficial, and increasing numbers of studies point to significant risks associated with cholesterol-lowering drugs.

For example, a 2008 paper published in the American Journal of Cardiovascular Drugs1 cites nearly 900 studies on the adverse effects of HMG-CoA reductase inhibitors (statins), which run the gamut from muscle problems to increased cancer risk.

How Do PCSK9 Inhibitors Work?

Whereas statins (HMG-CoA reductase inhibitors) reduce your cholesterol by blocking an enzyme in your liver that is responsible for making cholesterol, these newer drugs, PCSK9 inhibitors, target and suppress a particular gene involved in the regulation of how much cholesterol your liver can actually filter out.

Researchers discovered that people with underactive PCSK9 genes had low levels of LDL. They also had low levels of cardiovascular disease. Since high cholesterol has long been mistaken as a primary cause of cardiovascular disease, these findings were akin to striking scientific gold… As reported in the featured article2:

“It’s this discovery that has Sanofi and two other major drug companies, Amgen and Pfizer, racing to develop a drug that mimics the gene’s effects. The best approach, experts say, will be through monoclonal antibodies: antibodies that are created in a lab and help your immune system fight a disease or, in this case, fight cholesterol…

‘This is not to replace statin therapy,’ said Joe Miletich, senior vice president of research and development at Amgen. ‘This is actually to get patients to (their) goal who can’t get there.’… ‘With a statin medication, you can often get somebody’s cholesterol between 70 and 100 mg/dL,’ said Dr. Elliott Antman, president-elect of the American Heart Association and a dean at Harvard Medical School. ‘If you use these monoclonal antibodies, you could see a number way less than 50.'”

I’ve told you before that the odds are very high— greater than 100 to 1—that if you’re taking a statin, you don’t really need it. From my review, the only subgroup that might benefit are those born with a genetic defect called familial hypercholesterolemia, as this makes them resistant to traditional measures of normalizing cholesterol.

In my view, this warning is just as applicable when it comes to PCSK9 inhibitors. Your body needs cholesterol and it doesn’t matter how you lower it: statins, PCSK inhibitors, or diet and exercise like I did. If your cholesterol drops too low, you will suffer health problems that I review in the next section.

The Health Hazards of Having Too Little Cholesterol

Your body needs cholesterol for the production of cell membranes, hormones, vitamin D, and bile acids that help you to digest fat. It’s not hard to see then why too little cholesterol can have such detrimental effects on your body—especially your brain, where it helps your brain form memories and is vital to your neurological function.

For example, research published in 20083 showed that low HDL is associated with poor memory and decline in memory in middle-aged adults. If you value your brain and want to keep it functioning into your senior years, you’d be well advised to pay attention to what it needs, and that includes cholesterol, along with healthful fats like omega-3. But impaired memory and dementia are just the tip of the iceberg when it comes to low cholesterol’s impact on your brain. If your levels get too low, you also increase your risk of:

Even more importantly, heart disease may in fact be a sign of cholesterol deficiency, according to MIT researcher, Dr. Stephanie Seneff. Considering the fact that conventional medicine has been telling us that heart disease is due to elevated cholesterol and recommends lowering cholesterol levels as much as possible, Dr. Seneff’s claims may come as a complete shock to some.

“Heart disease, I think, is a cholesterol deficiency problem, and in particular a cholesterol sulfate deficiency problem…”

She points out that all of this information is available in the research literature, but it requires putting all the pieces together to see the full picture. Through her research, she believes that the mechanism we call “cardiovascular disease,” of which arterial plaque is a hallmark, is actually your body’s way to compensate for not having enough cholesterol sulfate. In a nutshell, high LDL appears to be a sign of cholesterol sulfate deficiency—it’s your body’s way of trying to maintain the correct balance by taking damaged LDL and turning it into plaque, within which the blood platelets produce the cholesterol sulfate your heart and brain needs for optimal function…

What this also means is that when you artificially lower your cholesterol with a statin drug, which effectively reduces that plaque but doesn’t address the root problem, your body is not able to compensate any longer, and as a result of lack of cholesterol sulfate you may end up with heart failure.

Have High Cholesterol? Address the Cause!

Contrary to popular belief, high cholesterol is not a disease in and of itself. It is actually a response to something gone awry in your body. Cholesterol is produced whenever your cells become damaged, as it’s a necessary component in making new, healthy cells, so if you have a lot of damaged cells, you’re also going to have a lot of cholesterol in your bloodstream. This is a sign that your cells need, and are, being repaired. While most conventional doctors do not recognize this sign for what it is and put you on toxic cholesterol-lowering drugs, a more knowledgeable doctor will address the root problem, which is typically related to chronic inflammation brought on by:

  • A diet too high in sugar/fructose and grains
  • Too many processed, overcooked foods
  • Lack of exercise
  • Emotional stress
  • Smoking

The remedy involves, of course, addressing these factors by making simple lifestyle changes that are outlined in my optimizednutrition and lifestyle plan. Whatever you do, don’t fall for the mistaken belief that the lower your cholesterol goes, the better. If you lower your cholesterol through artificial means without addressing the underlying causes for your elevated cholesterol levels, your body will continue to degenerate. Leave the decision of how much cholesterol your body needs up to your body, and make the right lifestyle choices to keep your cells in their top condition. This way you get the best of both worlds: the right amount of cholesterol and a body in tip-top shape.

The Many Well-Known Health Hazards of Statin Drugs

First, if you are a woman, it’s critical for you to know that statins are classified as a “pregnancy Category X medication” meaning,it causes serious birth defects, and should NEVER be used if you’re pregnant or planning a pregnancy. Last year, the US Food and Drug Administration5 (FDA) also announced it’s considering additional warning labels for statin drugs. Among them are warnings that statins may increase your risk of:

  • Liver damage
  • Memory loss and confusion
  • Type 2 diabetes
  • Muscle weakness (for certain statins)

In all, statin drugs have been directly linked to over 300 side effects6, including:

Cognitive loss Neuropathy Anemia
Acidosis Frequent fevers Cataracts
Sexual dysfunction An increase in cancer risk Pancreatic dysfunction
Immune system suppression Muscle problems, polyneuropathy (nerve damage in the hands and feet), and rhabdomyolysis, a serious degenerative muscle tissue condition Hepatic dysfunction (Due to the potential increase in liver enzymes, patients must be monitored for normal liver function)

Statins Cause Hallmark Symptoms of Heart Disease and Diabetes

Sadly, while millions of people are told to use statin drugs as a form of “preventive medicine” to protect their heart health, research shows that these drugs actually can have significantly detrimental effects on your heart! How is that preventive medicine? For example, a study published just last year in the journal Atherosclerosis7 showed that statin use is associated with a 52 percent increased prevalence and extent of calcified coronary plaque compared to non-users. And coronary artery calcification is the hallmark of potentially lethal heart disease!

Statins can also:

  • Deplete your body of CoQ10, which accounts for many of its devastating health effects. CoQ10 is used by every cell in your body, but especially your heart cells. Cardiac muscle cells have up to 200 times more mitochondria, and hence 200 times higher CoQ10 requirements than skeletal muscle. Therefore, if you take a statin, you must take supplemental CoQ10, or better, the reduced form called ubiquinol.

A recent study in the European Journal of Pharmacology8 showed that ubiquinol effectively rescued cells from the damage caused by the statin drug simvastatin, thereby protecting muscle cells from myopathies. Again demonstrating the necessity of CoQ10 supplementation during statin therapy, a recent study9 evaluating the benefits of CoQ10 and selenium supplementation for patients with statin-associated myopathy found that, compared to those given a placebo, the treatment group experienced significantly less pain, decreased muscle weakness and cramps, and less fatigue.

  • Interfere with the mevalonate pathway, which is the central pathway for the steroid management in your body. Products of this pathway that are negatively affected by statins include sex hormones, cortisone, the dolichols (which are involved in keeping the membranes inside your cells healthy), and all sterols, including cholesterol and vitamin D (which is similar to cholesterol and is produced from cholesterol in your skin).
  • Increase your insulin resistance, which contributes to chronic inflammation in your body. Increased insulin resistance can lead to heart disease, which, ironically, is the primary reason for taking a cholesterol-reducing drug in the first place. It can also promote belly fat, high blood pressure, heart attacks, chronic fatigue, thyroid disruption, and diseases like Parkinson’s, Alzheimer’s, and cancer.
  • Increase your risk of diabetes by raising your blood sugar. When you eat a meal that contains starches and sugar, some of the excess sugar goes to your liver, which then stores it away as cholesterol and triglycerides. Statins work by preventing your liver from making cholesterol. As a result, your liver returns the sugar to your bloodstream, which raises your blood sugar levels.

Drug-induced diabetes and genuine type 2 diabetes are not necessarily identical. If you’re on a statin drug and find that your blood glucose is elevated, it’s possible that what you have is just hyperglycemia—a side effect, and the result of your medication. Unfortunately, many doctors will at that point mistakenly diagnose you with “type 2 diabetes,” and possibly prescribe another drug, when all you may need to do is simply discontinue the statin in order for your blood glucose levels to revert back to normal.

Beware: Statins Can Also Completely Negate Your Fitness Efforts

One of the major benefits of exercise is the beneficial impact it has on your heart health, and exercise is a primary strategy to naturally maintain healthy cholesterol levels. Alas, researchers recently discovered that if you take a statin drug, you’re likely to forfeit most if not all health benefits of your exercise. In fact, the study, published in the Journal of the American College of Cardiology10, discovered that statin use led to dramatically reduced fitness benefits from exercise, in some cases actually making the volunteer LESS fit than before!

The key to understanding why statins prevent your body from reaping the normal benefits from exercise lies in understanding what these drugs do to your mitochondria—the energy chamber of your cells, responsible for the utilization of energy for all metabolic functions. As mentioned above, the primary fuel for your mitochondria is Coenzyme Q10 (CoQ10), and one of the primary mechanisms of harm from statins in general appears to be related to CoQ10 depletion.

A 2011 review published in Applied Physiology, Nutrition and Metabolism11 pointed out that exercise actually induces changes in mitochondrial enzyme content and activity, which can increase your cellular energy production and in so doing decrease your risk of chronic disease. The fact that statin drugs deplete your body of the primary fuel for your mitochondria helps explain why certain statin users in the trial ended up with worse aerobic fitness after a steady fitness regimen. There simply wasn’t enough mitochondrial fuel in their system.

To Evaluate Your Heart Disease Risk, Get the Right Tests Done

If your physician is urging you to check your total cholesterol, then you need to be aware that this test will tell you virtually nothingabout your risk of heart disease, unless it is 330 or higher.

One of the most important tests you can get to determine your real heart disease risk is the NMR LipoProfile, which measures your LDL particle number. This test also has other markers that can help determine if you have insulin resistance, which is a primary cause of elevated LDL particle number and increased heart disease risk. The NMR LipoProfile test easy to get and all major labs offer it. Most insurance policies cover the test as well. Best of all, even if your doctor were to refuse to order it, you can order it yourself via third-party intermediaries like Direct Labs, or you can order the test online, and get blood drawn locally. Two other ratios you should pay attention to are your:

  • HDL/Total Cholesterol Ratio: (i.e. take your HDL number and divide it by your total cholesterol number.) This should ideally be above 24 percent. If below 10 percent, you have a significantly elevated risk for heart disease.
  • Triglyceride/HDL Ratio: Should be below 2.

I have seen a number of people with total cholesterol levels over 250 who were actually at low risk for heart disease due to their elevated HDL levels. Conversely, I have seen many people with cholesterol levels under 200 who had a very high risk of heart disease, based on their low HDL. For four additional risk factors for heart disease that do not involve your cholesterol levels, please see my recent article: Side Effects of Statins.

How to Optimize Your Cholesterol Levels Naturally

The most effective way to optimize your cholesterol profile and prevent heart disease is via diet and exercise. Seventy-five percent of your cholesterol is produced by your liver, which is influenced by your insulin levels. Therefore, if you optimize your insulin level, you will automatically optimize your cholesterol and reduce your risk of both diabetes and heart disease.

There is NO drug that can cure heart disease, as the underlying cause is insulin and leptin resistance and arterial wall damage—both of which are caused by eating excessive amounts of sugars, grains, and especially fructose. So, in addition to regular exercise, my primary recommendations for safely regulating your cholesterol and reducing your risk of heart disease include:

  • Reduce, with the plan of eliminating grains and fructose from your diet. This is one of the best ways to optimize your insulin levels, which will have a positive effect on not just your cholesterol, but also reduces your risk of diabetes and heart disease, and most other chronic diseases. Use my Nutrition Plan to help you determine the ideal diet for you, and consume a good portion of your food raw.
  • Start intermittent fasting, which will radically improve your ability to burn fat as your primary fuel and thus help improve your insulin and leptin signaling.
  • Get plenty of high-quality, animal-based omega 3 fats, such as krill oil, and reduce your consumption of damaged omega-6 fats (trans fats, vegetable oils) to balance out your omega-3 to omega-6 ratio.
  • Include heart-healthy foods in your diet, such as olive oil, coconut and coconut oil, organic raw dairy products and eggs, avocados, raw nuts and seeds, and organic grass-fed meats.
  • Optimize your vitamin D levels by getting proper sun exposure or using a safe tanning bed.
  • Optimize your gut flora, as recent research suggests the bacterial balance in your intestines may play a role in your susceptibility to heart disease as well.
  • Walk barefoot to ground yourself to the earth. Lack of grounding has a lot to do with the rise of modern diseases as it affects inflammatory processes in your body. Grounding thins your blood, making it less viscous. Virtually, every aspect of cardiovascular disease has been correlated with elevated blood viscosity.

When you ground to the earth, your zeta potential quickly rises, which means your red blood cells have more charge on their surface, which forces them apart from each other. This action causes your blood to thin and flow easier. By repelling each other, your red blood cells are also less inclined to stick together and form a clot.

Take Control of Your Health

The odds are very high that if you’re taking cholesterol-lowering medication, you’re wasting your money and taking unnecessary risks with your health. From my review, the ONLY subgroup that might benefit from statins are those born with a genetic defect called familial hypercholesterolemia, as this makes them resistant to traditional measures of normalizing cholesterol, which I reviewed above.

Remember, your body needs cholesterol for the production of cell membranes, hormones, and vitamin D, just to mention a few. Cholesterol is also vital to your neurological function. And there’s strong evidence that having too little cholesterol increases your risk for cancer, memory loss, Parkinson’s disease, hormonal imbalances, stroke, depression, suicide, and violent behavior.

Taking a drug that can reduce your cholesterol levels down to 50 or below is absolutely a recipe for disaster, when you consider all your biological functions that need cholesterol!

Also keep in mind that contrary to what you’ve been told by pharmaceutical PR firms, statins have nothing to do with reducing your heart disease risk. In fact, this class of drugs can increase your heart disease risk—especially if you do not take Ubiquinol(CoQ10) along with it to mitigate the depletion of CoQ10 caused by the drug. So please, carefully weigh the risks and benefits!

Poor lifestyle choices are primarily to blame for elevated cholesterol levels, such as too much sugar, too little exercise, lack of sun exposure and never grounding to the earth. These are all things that are within your control, and don’t cost much (if any) money to address. If you have a genetic defect, medication may be needed. If you don’t, you may be surprised at how quickly and easily your cholesterol levels will normalize when you start implementing the required lifestyle changes.

If you’re currently taking a statin drug and are worried about the excessive side effects they cause, please consult with a knowledgeable health care practitioner who can help you to optimize your heart health naturally, without the use of these dangerous drugs.


Quality improvement initiatives required to reduce repeat lipid testing.

One-third of patients with coronary heart disease who reached target LDL levels underwent repeat lipid panels, suggesting that quality improvement efforts are needed to decrease unnecessary testing.

Salim S. Virani, MD, PhD, of the Michael E. DeBakey VA Medical Center and a researcher at the Health Services Research and Development Center of Excellence in Houston, and colleagues evaluated the number of patients with LDL levels lower than the Adult Treatment Panel III (ATP III) guideline-recommended LDL treatment target of 100 mg/dL who underwent repeat lipid testing within 11 months without medication intensification. They used data from patients with CHD in a VA network of seven medical centers with associated community-based outpatient clinics.

 “In these patients, repeat lipid testing may represent health resource overuse and possibly waste of health care resources,” the researchers wrote.

Potential waste of resources

Virani and colleagues identified 27,947 patients with CHDand LDL levels less than 100 mg/dL — 9,200 (32.9%) of whom underwent repeat lipid testing without intensification of treatment during the next 11 months. This translated to 12,686 repeat panels, with a mean of 1.38 additional tests per patient, according to study results.

“With a mean lipid panel cost of $16.08 based on Veterans Health Administration laboratory cost data, this is equivalent to $203,990 in annual costs for one VA network,” the researchers wrote.

“These results represent health care resource overuse and possibly their waste,” Virani told Cardiology Today. “Apart from the costs associated with these lipid panels, this also carries with it the cost for the patient’s time to undergo a repeat blood test and cost for the health care provider’s time to follow-up on these results after redundant testing and to inform the patient about these results.”

After adjustment for facility level clustering, data showed that those with a history of diabetes (OR=1.16; 95% CI, 1.10-1.22), hypertension (OR=1.21; 95% CI, 1.13-1.30), higher burden of illness (OR=1.39; 95% CI, 1.23-1.57) and more frequent primary care visits (OR=1.32; 95% CI, 1.25-1.39) had higher odds of undergoing repeat testing. In contrast, patients treated at a teaching facility (OR=0.74; 95% CI, 0.69-0.80) or from a physician provider (OR=0.93; 95% CI, 0.88-0.98) and patients with a medication possession ratio of 0.8 or higher (OR=0.75; 95% CI, 0.71-0.80) were less likely to have a repeat lipid panel.

The researchers also assessed 13,114 patients with CHD who met the ATP III optional treatment target of less than 70 mg/dL. In this population, 8,177 (62.4%) with LDL levels less than 70 mg/dL underwent repeat lipid testing during 11-month follow-up.

“This represents an area of redundant testing in patients and represents an opportunity to improve health care efficiency and reduce health care waste,” Virani said.


In an invited commentary, Joseph P. Drozda Jr., MD, of the Center for Innovative Care, Mercy, in Chesterfield, Mo., lauded the researchers’ study, noting that, with the implementation of electronic health records, future reports will likely identify other areas that require improvement and where waste can be reduced.

“This well-conceived study on a large clinical database, which has the advantage of containing pharmacy data for use in tracking medication adherence, delivers an important message regarding a type of waste that is likely widespread in health care and that goes under the radar because it involves a low-cost test. However, it is precisely these low-cost, high-volume tests and procedures that need to be addressed if significant saves from reduction of waste are to be realized,” he wrote.

For more information:

Drozda JP. JAMA Intern Med. 2013;doi:10.1001/jamainternmed.2013.6808.

Virani SS. JAMA Intern Med. 2013;doi:10.1001/jamainternmed/2013.8198.

Source: Endocrine Today



Risk of incident diabetes among patients treated with statins: population based study.


Objective To examine the risk of new onset diabetes among patients treated with different HMG-CoA reductase inhibitors (statins).

Design Population based cohort study with time to event analyses to estimate the relation between use of particular statins and incident diabetes. Hazard ratios were calculated to determine the effect of dose and type of statin on the risk of incident diabetes.

Setting Ontario, Canada.

Participants All patients aged 66 or older without diabetes who started treatment with statins from 1 August 1997 to 31 March 2010. The analysis was restricted to new users who had not been prescribed a statin in at least the preceding year. Patients with established diabetes before the start of treatment were excluded.

Interventions Treatment with statins.

Main outcome measure Incident diabetes.

Results Compared with pravastatin (the reference drug in all analyses), there was an increased risk of incident diabetes with atorvastatin (adjusted hazard ratio 1.22, 95% confidence interval 1.15 to 1.29), rosuvastatin (1.18, 1.10 to 1.26), and simvastatin (1.10, 1.04 to 1.17). There was no significantly increased risk among people who received fluvastatin (0.95, 0.81 to 1.11) or lovastatin (0.99, 0.86 to 1.14). The absolute risk for incident diabetes was about 31 and 34 events per 1000 person years for atorvastatin and rosuvastatin, respectively. There was a slightly lower absolute risk with simvastatin (26 outcomes per 1000 person years) compared with pravastatin (23 outcomes per 1000 person years). Our findings were consistent regardless of whether statins were used for primary or secondary prevention of cardiovascular disease. Although similar results were observed when statins were grouped by potency, the risk of incident diabetes associated with use of rosuvastatin became non-significant (adjusted hazard ratio 1.01, 0.94 to 1.09) when dose was taken into account.

Conclusions Compared with pravastatin, treatment with higher potency statins, especially atorvastatin and simvastatin, might be associated with an increased risk of new onset diabetes.


In this population based study, we found that patients treated with atorvastatin, rosuvastatin, or simvastatin were at increased risk of new onset diabetes compared with those treated with pravastatin. No such risk was evident with fluvastatin or lovastatin. The risk associated with rosuvastatin could depend on dose and duration of treatment. The risk of incident diabetes was similar whether statins were being used for primary or secondary prevention.

Overall, we observed a 10-22% increased risk of diabetes for some statins that is consistent with findings from previously published meta-analyses of clinical trials. The increased risk with rosuvastatin significantly decreased after covariate adjustment and became non-significant once dose was taken into consideration. This could possibly represent greater use of rosuvastatin in patients with lower cardiovascular risk.3 In 2009, an analysis of five placebo controlled trials (n=57 593) found a 13% (relative risk 1.13, 95% confidence interval 1.03 to 1.23) increased incidence of diabetes in people taking statins compared with placebo over an average 3.9 years of follow-up,9 with a subsequent analysis of 13 placebo controlled trials (n=91 140) showing a 9% (odds ratio 1.09, 95% confidence interval 1.02 to 1.17) increased incidence of diabetes over four years of follow-up.10 More recently, two meta-analyses have suggested a dose dependent effect for patients receiving high dose atorvastatin or simvastatin treatment versus moderate dose treatment (odds ratio 1.12, 95% confidence interval 1.04 to 1.22) and when considering only atorvastatin trials.11 12 Our results differ from those of the Women’s Health Initiative study, which showed a nearly 50% increase in new onset diabetes with statins compared with placebo (hazard ratio 1.48, 95% confidence interval 1.38 to 1.59), with no differential risk among low potency (fluvastatin, lovastatin, pravastatin) and high potency (simvastatin, atorvastatin) statins.14 Our findings, however, are consistent with the findings of Zaharan and colleagues in 2012, who found an increased risk with atorvastatin (hazard ratio 1.25, 1.21 to 1.28), rosuvastatin (1.42, 1.33 to 1.52), and simvastatin (1.14, 1.06 to 1.23).30 Our population based assessment adds to the discussion of risk when doctors are considering starting statin treatment in a patient for primary versus secondary prevention.

Possible mechanisms

Several factors could explain the increased risk of new onset diabetes among patients receiving certain statins.2 7 15 The increased production of plasma derived low density lipoprotein (LDL) cholesterol as a compensatory response to de novo cholesterol synthesis inhibition might result in direct inflammation and oxidation within the β cell. Consequently, the functional and structural integrity of β cells is compromized, impairing insulin secretion as a result of cellular apoptosis.15Additionally, metabolic receptor effects interfere with cellular glucose uptake, energy production, and insulin secretion.2 7 15 16 Statins can also inhibit calcium mediated pancreatic insulin release and decrease expression of the β cell glucose transporters GLUT-2 and GLUT-4.15 Finally, statins are also known to interfere with the synthesis of ubiquinone (CoQ10), which could independently alter insulin secretion.15 16 The degree to which statins are involved in these respective mechanisms of diabetes onset is variable and supports why some statins pose a higher risk than pravastatin.7 As shown in our dose and potency analyses, the risk could be greater for atorvastatin and simvastatin, regardless of the dose prescribed.

Limitations and strengths

Some limitations of our study merit emphasis. We could not identify and account for potentially important risk factors for diabetes such as weight, ethnicity, and family history. Newer statins might be preferentially used in patients at higher risk of diabetes, though the characteristics of patients in our study were highly similar across study groups. Secondly, data on blood lipids, hemoglobin A1C concentration, or triglyceride concentrations were unavailable, and therefore we could not use these measures for risk stratification or diagnostic purposes. The ODD, however, has been shown to be both sensitive (86-90%) and specific (92-97%).19 Furthermore, we had no data on marketing or promotional efforts nor did we have data on physicians’ preferences for particular statins. Although the statin groups were well balanced with respect to a wide variety of demographic and clinical variables, we cannot exclude the possibility of residual confounding.

Our study also had several strengths including a large sample size, use of pravastatin as an active comparator reference group, and a population based design. Our findings suggest that older patients treated with certain statins are at increased risk for incident diabetes, regardless of dose or whether treatment is used for primary or secondary prevention. The risk seems to be greatest with atorvastatin, rosuvastatin, and simvastatin. After adjustment for dose, however, the risk did not seem to persist among rosuvastatin users. Clinicians should consider this risk when they are contemplating statin treatment for individual patients. Preferential use of pravastatin, and potentially fluvastatin or lovastatin, while recognizing the limited efficacy data and increased risk of drug interactions with these two agents, might be warranted. Pravastatin might have a preferential benefit among primary prevention patients at high risk of diabetes.

What is already known on this topic

  • Given the widespread use of statins to manage hypercholesterolemia, small effects in their efficacy and safety profiles can have important population impact.
  • Statins have previously been associated with an increased risk of incident diabetes, though there is controversy around whether this risk differs among drugs
  • When compared with pravastatin, atorvastatin, rosuvastatin, and simvastatin are associated with a greater risk of new onset diabetes, regardless of their use for primary or secondary prevention of cardiovascular events
  • The risk for rosuvastatin users might depend on the dose prescribed

What this study adds



Source: BMJ


Gastric banding led to improvements in HDL, particle size after 5 years.

Bariatric surgery using gastric banding did not improve LDL cholesterol or LDL particle number or size, despite significant weight loss among patients who underwent the procedure. Results suggest, however, a beneficial HDL remodeling process based on a significant increase in HDL cholesterol and HDL particle size.

Researchers from the New York University Langone Medical Center said the HDL remodeling process persisted up to 5 years after gastric banding.

“Knowing that some studies suggest early improvements in lipids after bariatric surgery, there is a paucity of data regarding changes in the lipoprotein abnormalities characteristic of the dyslipidemia of obesity. What we sought to do was to determine both initial and long-term effects of gastric banding surgery on lipids, with attention to LDL and HDL characteristics,” researcherAmita Singh, MD, from NYU Langone Medical Center in New York, said during a presentation here.

Patients with a BMI of 30 to 40 (n=50) underwent laparoscopic gastric banding. Physical exams and blood samples for nuclear magnetic resonance spectroscopy were performed at baseline and at annual follow-up, which lasted 5 years.

At 1 and 5 years, researchers observed significant increases in HDL cholesterol (P<.001). After 5 years, mean HDL size was significantly increased (9.1 nm at baseline vs. 9.24 nm at 5 years; P<.002), and there was a trend toward increased HDL particle number (33.49 nm/L at baseline vs. 36.75 nm/L; P=.064). Conversely, early reductions in LDL particle number and size were nonsignificant after 5 years.

Metabolic syndrome and percent BMI loss had no effect on changes in particle number or size for both LDL and HDL. However, LDL particle number and LDL cholesterol were significantly correlated at 5 years (P<.001), although HDL cholesterol and HDL particle number were not, the researchers wrote. – by Samantha Costa

  • This study was interesting in the fact that we didn’t see a lot of the changes we expected. Acute weight loss lowers your cholesterol, but losing weight doesn’t lower your cholesterol, and it’s often just dietary changes. It’s interesting to see that, but it’s also limited.
  • Donna M. Polk, MD, MPH
  • Physician at Hartford Hospital (Connecticut)


  • Source: Endocrine Today.