How Statins Really Work Explains Why They Don't Really Work.

by Stephanie Seneff

1. Introduction

The statin industry has enjoyed a thirty year run of steadily increasing profits, as they find ever more ways to justify expanding the definition of the segment of the population that qualify for statin therapy. Large, placebo-controlled studies have provided evidence that statins can substantially reduce the incidence of heart attack. High serum cholesterol is indeed correlated with heart disease, and statins, by interfering with the body's ability to synthesize cholesterol, are extremely effective in lowering the numbers. Heart disease is the number one cause of death in the U.S. and, increasingly, worldwide. What's not to like about statin drugs?

I predict that the statin drug run is about to end, and it will be a hard landing. The thalidomide disaster of the 1950's and the hormone replacement therapy fiasco of the 1990's will pale by comparison to the dramatic rise and fall of the statin industry. I can see the tide slowly turning, and I believe it will eventually crescendo into a tidal wave, but misinformation is remarkably persistent, so it may take years.

I have spent much of my time in the last few years combing the research literature on metabolism, diabetes, heart disease, Alzheimer's, and statin drugs. Thus far, in addition to posting essays on the web, I have, together with collaborators, published two journal articles related to metabolism, diabetes, and heart disease (Seneff1 et al., 2011), and Alzheimer's disease (Seneff2 et al., 2011). Two more articles, concerning a crucial role for cholesterol sulfate in metabolism, are currently under review (Seneff3 et al., Seneff4 et al.). I have been driven by the need to understand how a drug that interferes with the synthesis of cholesterol, a nutrient that is essential to human life, could possibly have a positive impact on health. I have finally been rewarded with an explanation for an apparent positive benefit of statins that I can believe, but one that soundly refutes the idea that statins are protective. I will, in fact, make the bold claim that nobody qualifies for statin therapy, and that statin drugs can best be described as toxins.

2. Cholesterol and Statins

I would like to start by reexamining the claim that statins cut heart attack incidence by a third. What exactly does this mean? A meta study reviewing seven drug trials, involving in total 42,848 patients, ranging over a three to five year period, showed a 29% decreased risk of a major cardiac event (Thavendiranathan et al., 2006). But because heart attacks were rare among this group, what this translates to in absolute terms is that 60 patients would need to be treated for an average of 4.3 years to protect one of them from a single heart attack. However, essentially all of them will experience increased frailty and mental decline, a subject to which I will return in depth later on in this essay.

The impact of the damage due to the statin anti-cholesterol mythology extends far beyond those who actually consume the statin pills. Cholesterol has been demonized by the statin industry, and as a consequence Americans have become conditioned to avoid all foods containing cholesterol. This is a grave mistake, as it places a much bigger burden on the body to synthesize sufficient cholesterol to support the body's needs, and it deprives us of several essential nutrients. I am pained to watch someone crack open an egg and toss out the yolk because it contains "too much" cholesterol. Eggs are a very healthy food, but the yolk contains all the important nutrients. After all, the yolk is what allows the chick embryo to mature into a chicken. Americans are currently experiencing widespread deficiencies in several crucial nutrients that are abundant in foods that contain cholesterol, such as choline, zinc, niacin, vitamin A and vitamin D.

Cholesterol is a remarkable substance, without which all of us would die. There are three distinguishing factors which give animals an advantage over plants: a nervous system, mobility, and cholesterol. Cholesterol, absent from plants, is the key molecule that allows animals to have mobility and a nervous system. Cholesterol has unique chemical properties that are exploited in the lipid bilayers that surround all animal cells: as cholesterol concentrations are increased, membrane fluidity is decreased, up to a certain critical concentration, after which cholesterol starts toincrease fluidity (Haines, 2001). Animal cells exploit this property to great advantage in orchestrating ion transport, which is essential for both mobility and nerve signal transport. Animal cell membranes are populated with a large number of specialized island regions appropriately called lipid rafts. Cholesterol gathers in high concentrations in lipid rafts, allowing ions to flow freely through these confined regions. Cholesterol serves a crucial role in the non-lipid raft regions as well, by preventing small charged ions, predominantly sodium (Na+) and potassium (K+), from leaking across cell membranes. In the absence of cholesterol, cells would have to expend a great deal more energy pulling these leaked ions back across the membrane against a concentration gradient.

In addition to this essential role in ion transport, cholesterol is the precursor to vitamin D3, the sex hormones, estrogen, progesterone, and testosterone, and the steroid hormones such as cortisol. Cholesterol is absolutely essential to the cell membranes of all of our cells, where it protects the cell not only from ion leaks but also from oxidation damage to membrane fats. While the brain contains only 2% of the body's weight, it houses 25% of the body's cholesterol. Cholesterol is vital to the brain for nerve signal transport at synapses and through the long axons that communicate from one side of the brain to the other. Cholesterol sulfate plays an important role in the metabolism of fats via bile acids, as well as in immune defenses against invasion by pathogenic organisms.

Statin drugs inhibit the action of an enzyme, HMG coenzyme A reductase, that catalyses an early step in the 25-step process that produces cholesterol. This step is also an early step in the synthesis of a number of other powerful biological substances that are involved in cellular regulation processes and antioxidant effects. One of these is coenzyme Q10, present in the greatest concentration in the heart, which plays an important role in mitochondrial energy production and acts as a potent antioxidant (Gottlieb et al., 2000). Statins also interfere with cell-signaling mechanisms mediated by so-called G-proteins, which orchestrate complex metabolic responses to stressed conditions. Another crucial substance whose synthesis is blocked is dolichol, which plays a crucial role in the endoplasmic reticulum. We can't begin to imagine what diverse effects all of this disruption, due to interference with HMG coenzyme A reductase, might have on the cell's ability to function.

3. LDL, HDL, and Fructose

We have been trained by our physicians to worry about elevated serum levels of low density lipoprotein (LDL), with respect to heart disease. LDL is not a type of cholesterol, but rather can be viewed as a container that transports fats, cholesterol, vitamin D, and fat-soluble anti-oxidants to all the tissues of the body. Because they are not water-soluble, these nutrients must be packaged up and transported inside LDL particles in the blood stream. If you interfere with the production of LDL, you will reduce the bioavailability of all these nutrients to your body's cells.

The outer shell of an LDL particle is made up mainly of lipoproteins and cholesterol. The lipoproteins contain proteins on the outside of the shell and lipids (fats) in the interior layer. If the outer shell is deficient in cholesterol, the fats in the lipoproteins become more vulnerable to attack by oxygen, ever-present in the blood stream. LDL particles also contain a special protein called "apoB" which enables LDL to deliver its goods to cells in need. ApoB is vulnerable to attack by glucose and other blood sugars, especially fructose. Diabetes results in an increased concentration of sugar in the blood, which further compromises the LDL particles, by gumming up apoB. Oxidized and glycated LDL particles become less efficient in delivering their contents to the cells. Thus, they stick around longer in the bloodstream, and the measured serum LDL level goes up.

Worse than that, once LDL particles have finally delivered their contents, they become "small dense LDL particles," remnants that would ordinarily be returned to the liver to be broken down and recycled. But the attached sugars interfere with this process as well, so the task of breaking them down is assumed instead by macrophages in the artery wall and elsewhere in the body, through a unique scavenger operation. The macrophages are especially skilled to extract cholesterol from damaged LDL particles and insert it into HDL particles. Small dense LDL particles become trapped in the artery wall so that the macrophages can salvage and recycle their contents, and this is the basic source of atherosclerosis. HDL particles are the so-called "good cholesterol," and the amount of cholesterol in HDL particles is the lipid metric with the strongest correlation with heart disease, where less cholesterol is associated with increased risk. So the macrophages in the plaque are actually performing a very useful role in increasing the amount of HDL cholesterol and reducing the amount of small dense LDL.

The LDL particles are produced by the liver, which synthesizes cholesterol to insert into their shells, as well as into their contents. The liver is also responsible for breaking down fructose and converting it into fat (Collison et al., 2009). Fructose is ten times more active than glucose at glycating proteins, and is therefore very dangerous in the blood serum (Seneff1 et al., 2011). When you eat a lot of fructose (such as the high fructose corn syrup present in lots of processed foods and carbonated beverages), the liver is burdened with getting the fructose out of the blood and converting it to fat, and it therefore can not keep up with cholesterol supply. As I said before, the fats can not be safely transported if there is not enough cholesterol. The liver has to ship out all that fat produced from the fructose, so it produces low quality LDL particles, containing insufficient protective cholesterol. So you end up with a really bad situation where the LDL particles are especially vulnerable to attack, and attacking sugars are readily available to do their damage.

4. How Statins Destroy Muscles

Europe, especially the U.K., has become much enamored of statins in recent years. The U.K. now has the dubious distinction of being the only country where statins can be purchased over-the-counter, and the amount of statin consumption there has increased more than 120% in recent years (Walley et al, 2005). Increasingly, orthopedic clinics are seeing patients whose problems turn out to be solvable by simply terminating statin therapy, as evidenced by a recent report of three cases within a single year in one clinic, all of whom had normal creatine kinase levels, the usual indicator of muscle damage monitored with statin usage, and all of whom were "cured" by simply stopping statin therapy (Shyam Kumar et al., 2008). In fact, creatine kinase monitoring is not sufficient to assure that statins are not damaging your muscles (Phillips et al., 2002).

Since the liver synthesizes much of the cholesterol supply to the cells, statin therapy greatly impacts the liver, resulting in a sharp reduction in the amount of cholesterol it can synthesize. A direct consequence is that the liver is severely impaired in its ability to convert fructose to fat, because it has no way to safely package up the fat for transport without cholesterol (Vila et al., 2011). Fructose builds up in the blood stream, causing lots of damage to serum proteins.

The skeletal muscle cells are severely affected by statin therapy. Four complications they now face are: (1) their mitochondria are inefficient due to insufficient coenzyme Q10, (2) their cell walls are more vulnerable to oxidation and glycation damage due to increased fructose concentrations in the blood, reduced choleserol in their membranes, and reduced antioxidant supply, (3) there's a reduced supply of fats as fuel because of the reduction in LDL particles, and (4) crucial ions like sodium and potassium are leaking across their membranes, reducing their charge gradient. Furthermore, glucose entry, mediated by insulin, is constrained to take place at those lipid rafts that are concentrated in cholesterol. Because of the depleted cholesterol supply, there are fewer lipid rafts, and this interferes with glucose uptake. Glucose and fats are the main sources of energy for muscles, and both are compromised.

As I mentioned earlier, statins interfere with the synthesis of coenzyme Q10 (Langsjoen and Langsjoen, 2003), which is highly concentrated in the heart as well as the skeletal muscles, and, in fact, in all cells that have a high metabolic rate. It plays an essential role in the citric acid cycle in mitochondria, responsible for the supply of much of the cell's energy needs. Carbohydrates and fats are broken down in the presence of oxygen to produce water and carbon dioxide as by-products. The energy currency produced is adenosine triphosphate (ATP), and it becomes severely depleted in the muscle cells as a consequence of the reduced supply of coenzyme Q10.

The muscle cells have a potential way out, using an alternative fuel source, which doesn't involve the mitochondria, doesn't require oxygen, and doesn't require insulin. What it requires is an abundance of fructose in the blood, and fortunately (or unfortunately, depending on your point of view) the liver's statin-induced impairment results in an abundance of serum fructose. Through an anaerobic process taking place in the cytoplasm, specialized muscle fibers skim off just a bit of the energy available from fructose, and produce lactate as a product, releasing it back into the blood stream. They have to process a huge amount of fructose to produce enough energy for their own use. Indeed, statin therapy has been shown to increase the production of lactate by skeletal muscles (Pinieux et al, 1996).

Converting one fructose molecule to lactate yields only two ATP's, whereas processing a sugar molecule all the way to carbon dioxide and water in the mitochondria yields 38 ATP's. In other words, you need 19 times as much substrate to obtain an equivalent amount of energy. The lactate that builds up in the blood stream is a boon to both the heart and the liver, because they can use it as a substitute fuel source, a much safer option than glucose or fructose. Lactate is actually an extremely healthy fuel, water-soluble like a sugar but not a glycating agent.

So the burden of processing excess fructose is shifted from the liver to the muscle cells, and the heart is supplied with plenty of lactate, a high-quality fuel that does not lead to destructive glycation damage. LDL levels fall, because the liver can't keep up with fructose removal, but the supply of lactate, a fuel that can travel freely in the blood (does not have to be packaged up inside LDL particles) saves the day for the heart, which would otherwise feast off of the fats provided by the LDL particles. I think this is the crucial effect of statin therapy that leads to a reduction in heart attack risk: the heart is well supplied with a healthy alternative fuel.

This is all well and good, except that the muscle cells get wrecked in the process. Their cell walls are depleted in cholesterol because cholesterol is in such short supply, and their delicate fats are therefore vulnerable to oxidation damage. This problem is further compounded by the reduction in coenzyme Q10, a potent antioxidant. The muscle cells are energy starved, due to dysfunctional mitochondria, and they try to compensate by processing an excessive amount of both fructose and glucose anaerobically, which causes extensive glycation damage to their crucial proteins. Their membranes are leaking ions, which interferes with their ability to contract, hindering movement. They are essentially heroic sacrificial lambs, willing to die in order to safeguard the heart.

Muscle pain and weakness are widely acknowledged, even by the statin industry, as potential side effects of statin drugs. Together with a couple of MIT students, I have been conducting a study which shows just how devastating statins can be to muscles and the nerves that supply them (Liu et al, 2011). We gathered over 8400 on-line drug reviews prepared by patients on statin therapy, and compared them to an equivalent number of reviews for a broad spectrum of other drugs. The reviews for comparison were selected such that the age distribution of the reviewers was matched against that for the statin reviews. We used a measure which computes how likely it would be for the words/phrases that show up in the two sets of reviews to be distributed in the way they are observed to be distributed, if both sets came from the same probability model. For example, if a given side effect showed up a hundred times in one data set and only once in the other, this would be compelling evidence that this side effect was representative of that data set. Table 1 shows several conditions associated with muscle problems that were highly skewed towards the statin reviews.

I believe that the real reason why statins protect the heart from a heart attack is that muscle cells are willing to make an incredible sacrifice for the sake of the larger good. It is well acknowledged that exercise is good for the heart, although people with a heart condition have to watch out for overdoing it, walking a careful line between working out the muscles and overtaxing their weakened heart. I believe, in fact, that the reason exercise is good is exactly the same as the reason statins are good: it supplies the heart with lactate, a very healthy fuel that does not glycate cell proteins.

5. Membrane Cholesterol Depletion and Ion Transport

As I alluded to earlier, statin drugs interfere with the ability of muscles to contract through the depletion of membrane cholesterol. (Haines, 2001) has argued that the most important role of cholesterol in cell membranes is the inhibition of leaks of small ions, most notably sodium (Na+) and potassium (K+). These two ions are essential for movements, and indeed, cholesterol, which is absent in plants, is the key molecule that permits mobility in animals, through its strong control over ion leakage of these molecules across cell walls. By protecting the cell from ion leaks, cholesterol greatly reduces the amount of energy the cell needs to invest in keeping the ions on the right side of the membrane.

There is a widespread misconception that "lactic acidosis," a condition that can arise when muscles are worked to exahustion, is due to lactic acid synthesis. The actual story is the exact opposite: the acid build-up is due to excess breakdown of ATP to ADP to produce energy to support muscle contraction. When the mitochondria can't keep up with energy consumption by renewing the ATP, the production of lactate becomes absolutely necessary to preventacidosis (Robergs et al., 2004). In the case of statin therapy, excessive leaks due to insufficient membrane cholesterol require more energy to correct, and all the while the mitochondria are producing less energy.

In in vitro studies of phospholipid membranes, it has been shown that the removal of cholesterol from the membrane leads to a nineteen fold increase in the rate of potassium leaks through the membrane (Haines, 2001). Sodium is affected to a lesser degree, but still by a factor of three. Through ATP-gated potassium and sodium channels, cells maintain a strong disequilibrium across their cell wall for these two ions, with sodium being kept out and potassium being held inside. This ion gradient is what energizes muscle movement. When the membrane is depleted in cholesterol, the cell has to burn up substantially more ATP to fight against the steady leakage of both ions. With cholesterol depletion due to statins, this is energy it doesn't have, because the mitochondria are impaired in energy generation due to coenzyme-Q10 depletion.

Muscle contraction itself causes potassium loss, which further compounds the leak problem introduced by the statins, and the potassium loss due to contraction contributes significantly to muscle fatigue. Of course, muscles with insufficient cholesterol in their membranes lose potassium even faster. Statins make the muscles much more vulnerable to acidosis, both because their mitochondria are dysfunctional and because of an increase in ion leaks across their membranes. This is likely why athletes are more susceptible to muscle damage from statins (Meador and Huey, 2010, Sinzinger and O'Grady, 2004): their muscles are doubly challenged by both the statin drug and the exercise.

An experiment with rat soleus muscles in vitro showed that lactate added to the medium was able to almost fully recover the force lost due to potassium loss (Nielsen et al, 2001). Thus, production and release of lactate becomes essential when potassium is lost to the medium. The loss of strength in muscles supporting joints can lead to sudden uncoordinated movements, overstressing the joints and causing arthritis (Brandt et al., 2009). In fact, our studies on statin side effects revealed a very strong correlation with arthritis, as shown in the table.

While I am unaware of a study involving muscle cell ion leaks and statins, a study on red blood cells and plateletshas shown that there is a substantial increase in the Na+-K+-pump activity after just a month on a modest 10 mg/dl statin dosage, with a concurrent decrease in the amount of cholesterol in the membranes of these cells (Lohn et al., 2000). This increased pump activity (necessitated by membrane leaks) would require additional ATP and thus consume extra energy.

Muscle fibers are characterized along a spectrum by the degree to which they utilize aerobic vs anaerobic metabolism. The muscle fibers that are most strongly damaged by statins are the ones that specialize in anaerobic metabolism (Westwood et al., 2005). These fibers (Type IIb) have very few mitochondria, as contrasted with the abundant supply of mitochondria in the fully aerobic Type 1A fibers. I suspect their vulnerability is due to the fact that they carry a much larger burden of generating ATP to fuel the muscle contraction and to produce an abundance of lactate, a product of anaerobic metabolism. They are tasked with both energizing not only themselves but also the defective aerobic fibers (due to mitochondrial dysfunction) and producing enough lactate to offset the acidosis developing as a consequence of widespread ATP shortages.

6. Long-term Statin Therapy Leads to Damage Everywhere

Statins, then, slowly erode the muscle cells over time. After several years have passed, the muscles reach a point where they can no longer keep up with essentially running a marathon day in and day out. The muscles start literally falling apart, and the debris ends up in the kidney, where it can lead to the rare disorder, rhabdomyolysis, which is often fatal. In fact, 31 of our statin reviews contained references to "rhabdomyolysis" as opposed to none in the comparison set. Kidney failure, a frequent consequence of rhabdomyolysis, showed up 26 times among the statin reviews, as opposed to only four times in the control set.

The dying muscles ultimately expose the nerves that innervate them to toxic substances, which then leads to nerve damage such as neuropathy, and, ultimately Amyloid Lateral Sclerosis (ALS), also known as Lou Gehrig's disease, a very rare, debilitating, and ultimately fatal disease which is now on the rise due (I believe) to statin drugs. People diagnosed with ALS rarely live beyond five years. Seventy-seven of our statin reviews contained references to ALS, as against only 7 in the comparison set.

As ion leaks become untenable, cells will begin to replace the potassium/sodium system with a calcium/magnesium based system. These two ions are in the same rows of the periodic table as sodium/potassium, but advanced by one column, which means that they are substantially larger, and therefore it's much harder for them to accidentally leak out. But this results in extensive calcification of artery walls, heart valves, and the heart muscle itself. Calcified heart valves can no longer function properly to prevent backflow, and diastolic heart failure results from increased left ventricular stiffness. Research has shown that statin therapy leads to increased risk to diastolic heart failure (Silver et al., 2004, Weant and Smith, 2005). Heart failure shows up 36 times in our statin drug data as against only 8 times in the comparison group.

Once the muscles can no longer keep up with lactate supply, the liver and heart will be further imperilled. They're now worse off than they were before statins, because the lactate is no longer available, and the LDL, which would have provided fats as a fuel source, is greatly reduced. So they're stuck processing sugar as fuel, something that is now much more perilous than it used to be, because they are depleted in membrane cholesterol. Glucose entry into muscle cells, including the heart muscle, mediated by insulin, is orchestrated to occur at lipid rafts, where cholesterol is highly concentrated. Less membrane cholesterol results in fewer lipid rafts, and this leads to impaired glucose uptake. Indeed, it has been proposed that statins increase the risk to diabetes (Goldstein and Mascitelli, 2010, Hagedorn and Arora, 2010). Our data bear out this notion, with the probability of the observed distributions of diabetes references happening by chance being only 0.006.

7. Statins, Caveolin, and Muscular Dystrophy

Lipid rafts are crucial centers for transport of substances (both nutrients and ions) across cell membranes and as a cell signaling domain in essentially all mammalian cells. Caveolae ("little caves") are microdomains within lipid rafts, which are enriched in a substance called caveolin (Gratton et al., 2004). Caveolin has received increasing attention of late due to the widespread role it plays in cell signaling mechanisms and the transport of materials between the cell and the environment (Smart et al., 1999).

Statins are known to interfere with caveolin production, both in endothelial cells (Feron et al., 2001) and in heart muscle cells, where they've been shown to reduce the density of caveolae by 30% (Calaghan, 2010). People who have a defective form of caveolin-3, the version of caveolin that is present in heart and skeletal muscle cells, develop muscular dystrophy as a consequence (Minetti et al., 1998). Mice engineered to have defective caveolin-3 that stayed in the cytoplasm instead of binding to the cell wall at lipid rafts exhibited stunted growth and paralysis of their legs (Sunada et al., 2001). Caveolin is crucial to cardiac ion channel function, which, in turn, is essential in regulating the heart beat and protecting the heart from arrhythmias and cardiac arrest (Maguy et al, 2006). In arterial smooth muscle cells, caveolin is essential to the generation of calcium sparks and waves, which, in turn, are essential for arterial contraction and expansion, to pump blood through the body (Taggart et al, 2010).

In experiments involving constricting the arterial blood supply to rats' hearts, researchers demonstrated a 34% increase in the amount of caveolin-3 produced by the rat's hearts, along with a 27% increase in the weight of the left ventricle, indicating ventricular hypertrophy. What this implies is that the heart needs additional caveolin to cope with blocked vessels, whereas statins interfere with the ability to produce extra caveolin (Kikuchi et al., 2005).

8. Statins and the Brain

While the brain is not the focus of this essay, I cannot resist mentioning the importance of cholesterol to the brain and the evidence of mental impairment available from our data sets. Statins would be expected to have a negative impact on the brain, because, while the brain makes up only 2% of the body's weight, it houses 25% of the body's cholesterol. Cholesterol is highly concentrated in the myelin sheath, which encloses axons which transport messages long distances (Saher et al., 2005). Cholesterol also plays a crucial role in the transmission of neurotransmitters across the synapse (Tong et al, 2009). We found highly skewed distribution of word frequencies for dementia, Parkinson's disease, and short term memory loss, with all of these occurring much more frequently in the statin reviews than in the comparison reviews.

A recent evidence-based article (Cable, 2009) found that statin drug users had a high incidence of neurological disorders, especially neuropathy, parasthesia and neuralgia, and appeared to be at higher risk to the debilitating neurological diseases, ALS and Parkinson's disease. The evidence was based on careful manual labeling of a set of self-reported accounts from 351 patients. A mechanism for such damage could involve interference with the ability of oligodendrocytes, specialized glial cells in the nervous system, to supply sufficient cholesterol to the myelin sheath surrounding nerve axons. Genetically-engineered mice with defective oligodendrocytes exhibit visible pathologies in the myelin sheath which manifest as muscle twitches and tremors (Saher et al, 2005). Cognitive impairment, memory loss, mental confusion, and depression were also significantly present in Cable’s patient population. Thus, his analysis of 351 adverse drug reports was largely consistent with our analysis of 8400 reports.

9. Cholesterol's Benefits to Longevity

The broad spectrum of severe disabilities with increased prevalence in statin side effect reviews all point toward a general trend of increased frailty and mental decline with long-term statin therapy, things that are usually associated with old age. I would in fact best characterize statin therapy as a mechanism to allow you to grow old faster. A highly enlightening study involved a population of elderly people who were monitored over a 17 year period, beginning in 1990 (Tilvis et al., 2011). The investigators looked at an association between three different measures of cholesterol and manifestations of decline. They measured indicators associated with physical frailty and mental decline, and also looked at overall longevity. In addition to serum cholesterol, a biometric associated with the ability to synthesize cholesterol (lathosterol) and a biometric associated with the ability to absorb cholesterol through the gut (sitosterol) were measured.

Low values of all three measures of cholesterol were associated with a poorer prognosis for frailty, mental decline and early death. A reduced ability to synthesize cholesterol showed the strongest correlation with poor outcome. Individuals with high measures of all three biometrics enjoyed a 4.3 year extension in life span, compared to those for whom all measures were low. Since statins specifically interfere with the ability to synthesize cholesterol, it is logical that they would also lead to increased frailty, accelerated mental decline, and early death.

For both ALS and heart failure, survival benefit is associated with elevated cholesterol levels. A statistically significant inverse correlation was found in a study on mortality in heart failure. For 181 patients with heart disease and heart failure, half of those whose serum cholesterol was below 200 mg/dl were dead three years after diagnosis, whereas only 28% of the patients whose serum cholesterol was above 200 mg/dl had died. In another study on a group of 488 patients diagnosed with ALS, serum levels of triglycerides and fasting cholesterol were measured at the time of diagnosis (Dorstand et al., 2010). High values for both lipids were associated with improved survival, with a p-value < 0.05.

10. What to do Instead to Avoid Heart Disease

If statins don't work in the long run, then what can you do to protect your heart from atherosclerosis? My personal opinion is that you need to focus on natural ways to reduce the number of small dense LDL particles, which feed the plaque, and alternative ways to supply the product that the plaque produces (more about that in a moment). Obviously, you need to cut way back on fructose intake, and this means mainly eating whole foods instead of processed foods. With less fructose, the liver won't have to produce as many LDL particles from the supply side. From the demand side, you can reduce your body's dependency on both glucose and fat as fuel by simply eating foods that are good sources of lactate. Sour cream and yogurt contain lots of lactate, and milk products in general contain the precursor lactose, which gut bacteria will convert to lactate, assuming you don't have lactose intolerance. Strenuous physical exercise, such as a tread machine workout, will help to get rid of any excess fructose and glucose in the blood, with the skeletal muscles converting them to the much coveted lactate.

Finally, I have a set of perhaps surprising recommendations that are based on research I have done leading to the two papers that are currently under review (Seneff3 et al, Seneff4 et al.). My research has uncovered compelling evidence that the nutrient that is most crucially needed to protect the heart from atherosclerosis is cholesterol sulfate. The extensive literature review my colleagues and I have conducted to produce these two papers shows compellingly that the fatty deposits that build-up in the artery walls leading to the heart exist mainly for the purpose of extracting cholesterol from glycated small dense LDL particles and synthesizing cholesterol sulfate from it, providing the cholesterol sulfate directly to the heart muscle. The reason the plaque build-up occurs preferentially in the arteries leading to the heart is so that the heart muscle can be assured an adequate supply of cholesterol sulfate. In our papers, we develop the argument that the cholesterol sulfate plays an essential role in the caveolae in the lipid rafts, in mediating oxygen and glucose transport.

The skin produces cholesterol sulfate in large quantities when it is exposed to sunlight. Our theory suggests that the skin actually synthesizes sulfate from sulfide, capturing energy from sunlight in the form of the sulfate molecule, thus acting as a solar-powered battery. The sulfate is then shipped to all the cells of the body, carried on the back of the cholesterol molecule.

Evidence of the benefits of sun exposure to the heart is compelling, as evidenced by a study conducted to investigate the relationship between geography and cardiovascular disease (Grimes et al., 1996). Through population statistics, the study showed a consistent and striking inverse linear relationship between cardiovascular deaths and estimated sunlight exposure, taking into account percentage of sunny days as well as latitude and altitude effects. For instance, the cardiovascular-related death rate for men between the ages of 55 and 64 was 761 in Belfast, Ireland but only 175 in Toulouse, France.

Cholesterol sulfate is very versatile. It is water soluble so it can travel freely in the blood stream, and it enters cell membranes ten times as readily as cholesterol, so it can easily resupply cholesterol to cells. The skeletal and heart muscle cells make good use of the sulfate as well, converting it back to sulfide, and synthesizing ATP in the process, thus recovering the energy from sunlight. This decreases the burden on the mitochondria to produce energy. The oxygen released from the sulfate molecule is a safe source of oxygen for the citric oxide cycle in the mitochondria.

So, in my view, the best way to avoid heart disease is to assure an abundance of an alternative supply of cholesterol sulfate. First of all, this means eating foods that are rich in both cholesterol and sulfur. Eggs are an optimal food, as they are well supplied with both of these nutrients. But secondly, this means making sure you get plenty of sun exposure to the skin. This idea flies in the face of the advice from medical experts in the United States to avoid the sun for fear of skin cancer. I believe that the excessive use of sunscreen has contributed significantly, along with excess fructose consumption, to the current epidemic in heart disease. And the natural tan that develops upon sun exposure offers far better protection from skin cancer than the chemicals in sunscreens.

11. Concluding Remarks

Every individual gets at most only one chance to grow old. When you experience your body falling apart, it is easy to imagine that this is just due to the fact that you are advancing in age. I think the best way to characterize statin therapy is that it makes you grow older faster. Mobility is a great miracle that cholesterol has enabled in all animals. By suppressing cholesterol synthesis, statin drugs can destroy that mobility. No study has shown that statins improve all-cause mortality statistics. But there can be no doubt that statins will make your remaining days on earth a lot less pleasant than they would otherwise be.

To optimize the quality of your life, increase your life expectancy, and avoid heart disease, my advice is simple: spend significant time outdoors; eat healthy, cholesterol-enriched, animal-based foods like eggs, liver, and oysters; eat fermented foods like yogurt and sour cream; eat foods rich in sulfur like onions and garlic. And finally, say "no, thank-you" to your doctor when he recommends statin therapy.

References

Big pharma 'research' suggests all people over 50 should take statins every day for life

Long term use linked to debilitating illness and higher profits

The Pressure’s On: Preventing High Blood Pressure

Posted By Dr. Axe On December 2, 2009 @ 7:00 am In Heart Disease | 5 Comments

The “epidemics” associated with life in America are most often the result of the western diet and lifestyle. One of the precursors to a host of other epidemic conditions is hypertension or high blood pressure. Hypertension, as high blood pressure is also known, affects 30% of the American population and is a preventable condition. 

The Western lifestyle—diet, low physical activity levels and stress—contributes to a wide variety of chronic diseases and conditions in Americans. These conditions collectively afflict 65% of the adult population in the U.S., while they are rare in cultures that have been isolated from exposure to a western lifestyle.

In fact, as traditional societies begin to adopt western foods and lifestyles, their incidences of chronic conditions such as cancer, diabetes, heart disease, hypertension, obesity and osteoporosis ^[1] rose dramatically.

An example of this is found in the Canadian Inuit of Nunavik, Quebec. In September of 2009, Dr. Marie-Ludivine Chateau-Degat told the Canadian Cardiovascular Congress that the recent reach of Western foods has severely impacted the health of the natives. The traditional Inuit diet had consisted of fish, seafood, caribou, wild fowl and other marine mammal meat before 1992. The consumption of such a diet included physical labor and activity, the pooling of communal resources, social activities centered around the collective good and social ties, and a diet rich in unprocessed foods, sea salt and other nutrients.

By 2004, store-bought foods had mostly replaced the native diet. 95% of the sodium the Intuits’ now ingest comes from processed foods in the form of highly processed, iodized salt. The majority of carbohydrates they ingest come in the form of sugary drinks. Intake of dietary fiber and essential vitamins and minerals has plummeted, while hypertension, diabetes, heart disease and obesity have soared in the population.

Blood pressure

Most Americans don’t even realize they have high blood pressure until serious problems arise.

Blood pressure is a combination of systolic and diastolic pressure. Systolic pressure represents blood force or pressure while the heart is beating and diastolic pressure stands for blood pressure when the heart is at rest.

Systolic pressure is always the first or top measurement in a blood pressure reading. In a reading of 140/90, 140 represents systolic pressure and 90 represents diastolic pressure. 

In prehypertension, systolic numbers range from 120-139 and diastolic numbers range from 80-89. 

Stage 1 hypertension numbers vary from 140-159 for systolic values and 90-99 in diastolic numbers. 

With Stage 2 hypertension, systolic readings are 160 or higher and diastolic readings measure 100 or higher. 

Although both numbers are significant, after about age 50, the systolic number is most important. Only 10% of high blood pressure cases are due to secondary or identifiable causes such as medications or conditions and diseases of other organs.

Avoid These Like the Plague

High fructose corn syrup ^[2]? If you eat any packaged foods or sodas, most likely you do, and you’re also more likely to develop hypertension (among other problems) because of it. Americans consume 30% more sugar than they did just 20 years ago and 4 times as much as they did 100 years ago, before the advent of highly processed foods. The obesity rates then were less than 5%, while today 64.5% of American adults are overweight and 30.5% are obese.

Researchers studied 4,528 adults that had no prior history of hypertension.  Those who ingested more than 74 grams of added sugar (about the amount in 2 ½ sugary drinks) daily, led to 28%, 36% and 87% increased risk in high blood pressure readings over time. The percentages correspond to blood pressure readings of 135/85, 140/90 and 160/100.

Another study has looked at American sodium intake. Highly refined salt exists in large amounts in processed foods. The study predicted that reducing sodium intake could eliminate 11 million cases of high blood pressure and save the U.S. $32 billion annually.

Research estimates that more than 77% of America’s sodium intake comes in the form of processed foods rather than salt added to foods while cooking or eating at home. Fast food, another fixture of the western lifestyle, is loaded with sodium. Replace all processed and refined salt with natural sea salt.

Helpful Foods

Potassium: is a compound that seems to protect people from the development of hypertension. Supplements of potassium don’t work well according to research, but foods that contain them do.

Spinach: Spinach is rich in magnesium and folate which can help prevent high blood pressure and cardiovascular disease.

Sunflower Seeds: Rich in potassium, magnesium and healthy plant fats, sunflower seeds can help reduce cholesterol levels, opening up blood vessels and promoting healthy blood pressure.

Bananas: Bananas contain loads of potassium and fiber ^[3].

Healthy Fats: Oily, cold-water fish provides  omega-3 fatty acids, a healthy balancing technique to the overload of omega-6 and omega-9 fatty acids that are overly prevalent in processed foods, fast and convenient foods and much of the western diet.

Garlic: Research on the health benefits of garlic is finding more and more miraculous effects. Among them, garlic seems to help thin the blood, prevent the blockage in blood vessels, and so lower blood pressure.

Tomatoes: Tomatoes are loaded with calcium, potassium, vitamins A, C and E and lycopene. Compounds in tomatoes can lower cholesterol buildup in blood vessels and combat the development of hypertension in a variety of ways. Lycopene, one of the tomato’s most useful compounds, is activated by heat, so add tomatoes to your next chili or stew.

Broccoli: Broccoli has been found to have a whole host of beneficial health effects including high amounts of potassium and chromium that help regulate blood sugar levels and weight, both related to high blood pressure.

Melon: Melon is rich in potassium. Cantaloupe and watermelon are especially rich sources.

Lifestyle Aids

Regular exercise ^[4] and diet ^[5] play a large role in the development (or not) of hypertension. One of the most detrimental components of the western lifestyle is stress.Managing stress ^[6] includes relaxation techniques such as deep breathing, yoga, journaling or art therapy.

You can raise your blood pressure to alarming levels just by thinking or stressing about events. Imagined events have as much physiological effect as real ones. This is the basis of Post Traumatic Stress Disorder and the improvement of performance in businessmen and Olympic athletic gains with visualization.

The western lifestyle might include career and lifestyle choices that incite chronic disease but that doesn’t mean that you have to proscribe to them. Going against a cultural current takes strength, but the failure of our cultural norm has contributed to the splintering of its route and the availability of alternate paths.

The fight for a culture’s health depends less on science that focuses on finding magical cures in drugs, and more on making fundamental shifts in food production, availability, our connections to food, our work life and stress factors, and re-prioritizing values. The best preventative measure? A healthy lifestyle. It’s common sense, really. With this article and the others on this site, you are now equipped to truly maximize your health.

Dr. Axe's Action Steps

1. Stop the trips to the fast food drive-thru! Eliminate processed foods and sodas that are laden with sugar, high fructose corn syrup, refined salt and unhealthy fats.
2. Eat a wide variety of foods, focusing especially on adding more vegetables to your diet.
3. Supplement with 1 Tbsp. of cod liver oil or 1 salmon oil capsule daily and I-2 cloves of garlic daily.
4. Learn how to recognize and manage stress in your life. Consider making a vision board with your goals. Include pictures and strategies for achieving them.

Study finds that elderly with cholesterol less that 189 had a double risk of dying.

Physicians were informed to consider very low levels of cholesterol as potential warning signs of a serious disease or as signals of rapidly declining health.

A NEW APPROACH TO METABOLIC SYNDROME
By: Michael P. Ciell, R.Ph.,

The Greatest Healthcare/Financial Crisis

Metabolic Syndrome (aka Syndrome X) with its four hallmark symptoms of obesity, hypertension, dyslipidemia and hyperglycemia is devastating our country as well as the whole of North America. In March of 2005 the National Institutes of Health and the New England Journal of Medicine published a paper stating that because of this epidemic the current generation is projected to have a shorter life expectancy then the previous one…for the first time in recorded history! Since that paper things have become much worse. Worse, despite the fact we have changed the USDA “Food Pyramid”, developed many new classes of pharmaceutical agents (especially ones for pre-diabetes and diabetes Type II), have taken soda machines out of schools, and even the First Lady’s top priority is the obesity epidemic. This syndrome, with all of its comorbidities (cardiovascular disease, stroke, many cancers, kidney failure, blindness, amputations ,etc.), accounts for the majority of healthcare dollars spent. If the tide is not turned, Metabolic Syndrome will bankrupt our country. This is a fact.

The Pathophysiology of Metabolic Syndrome
In 1987 the late Gerald Reaven, MD, Professor of Medicine at Stanford University’s College of Medicine, first demonstrated that the four hallmark symptoms shared a commonality: hyper-insulinemia coupled with insulin resistance. He coined the term “Syndrome X” to illustrate the point: the four legs of the “X” represent the symptoms (hypertension, central obesity, hyperglycemia and dyslipidemia) and the nexus of the “X” being the causal agents of too much insulin along with insulin resistance (the cells’ do not respond to normal physiologic amounts of insulin). This is the standard, accepted medical model of this disease.

The Failure of Current Treatments
We are being ravaged by this syndrome due to the simple fact that we have ignored the model! Instead of focusing our attention on the root cause we have decided to treat each of the symptoms as separate, unrelated diseases. Thus we have new dietary recommendations and “diets d’Jour”, as well as a plethora of exercise regimens prescribed for obesity and of course, the “diet pills”. There too are the myriad of prescription drugs to ‘control’ the other three symptoms. If our attention is on ‘controlling symptoms’ we have admitted, by default, that there is NOTHING WE CAN DO FOR THE CAUSATIVE FACTORS and we will just have to LEARN TO LIVE WITH OUR DISEASE (i.e. ‘it will always be with us, we’ll just control it’). This attitude of acceptance is bad enough and unaffordable in the long run, but that’s the least of it. If we understand the pathophysiology of this syndrome we readily can see why many of these treatments actually make the other symptoms much worse! Hyper-insulinemia means the patient’s pancreas is secreting an exaggerated amount of insulin in response to rises in blood glucose. This can easily be confirmed by doing a fasting insulin level OR the standard glucose challenge test and ordering insulin levels along with glucose levels at time zero, one hour and two hour intervals post challenge glucose administration.

Sadly, the vast majority of practitioners do not even think about such an important marker. So we dwell on just the glucose level or Hemoglobin A1c (merely symptoms ) and prescribe drugs such as the sulfonylureas (i.e. glyburide, glipizide, glimperide) which cause the pancreas to secrete EVEN MORE INSULIN or we actually give them INSULIN ITSELF in an aggressive attempt to control a symptom. If the model is correct then this therapy should make the syndrome worse……and it does! This is the fundamental reason why we have failed to stem the tide (or actually reverse) this seemingly insidious malady.

The Concept of Homeostasis
If insulin just mediated glucose uptake by our cells and did nothing else, we probably would not have this problem. However this is not the case and when the amount of insulin remains consistently elevated it does other things…..and these things are NOT good. Before discussing the effects of hyper-insulinemia, a review of the fundamental concept of homeostasis should be addressed.

The body is an organism that strives to maintain a constant internal environment in the face of constantly changing, often hostile, external factors. Blood pressure, blood glucose, body temperature, acid / base balance, etc. must remain within a relatively narrow range in order to survive. It does so by means of the action/reaction principle, or mechanisms that exert opposite effects so that a balance may be
achieved. Examples are: vasodilation / vasoconstriction, oxidation / reduction, anabolism/catabolism, assimilation / elimination, etc. These systems are exquisitely regulated primarily by the nervous system and the endocrine (hormonal) system. So if the environmental temperature is 125 degrees, our internal temperature remains at 98.6 degrees. Likewise if the temperature drops to 20 degrees, certain mechanisms are in place to make certain our internal temperature remains a constant 98.6. Glucose homeostasis is essential for life as certain cells in the body can only use glucose as an energy source (certain brain cells, the adrenal medulla, red blood cells, etc.). Whether in times of feast or famine, blood glucose must remain in a certain range and insulin and glucagon are the master hormones that control this process (forget about ghrelin, leptin, incretins and all these ‘new mini-hormones’ that are in the literature today…these are subservient to the two masters). The body needs BOTH of these “master hormones” to maintain balance ( as they have exactly opposite physiological functions….if you know what insulin does, then you automatically know what glucagon does…the exact opposite!) and if an imbalance occurs, dysfunction or “disease” will arise.

The Physiological Effects of Insulin
Insulin’s primary function is mediating glucose uptake to muscle cells, and in this way, helps regulate blood glucose homeostasis. However insulin binds to many other receptors in the body and affects MANY other physiological parameters. And here’s the “rub”. If insulin receptors on the muscle cells become resistant to insulin’s effect (and do not uptake glucose in an effective manner) the pancreas will produce more to ensure glucose uptake will occur. But if we increase insulin levels, what happens to OTHER receptors that are not “resistant” yet and modulate other bodily functions? This scenario becomes way more complicated, in that, these receptors become ‘insulin resistant’ at different times. So a ‘typical Syndrome Xer’ presents to the physician with some central obesity, slightly elevated blood pressure, slightly elevated blood glucose and a less than stellar lipid panel. He is told to lose some weight by eating more fruits and vegetables, cut down on fats and cholesterol (have oatmeal instead of bacon and eggs) and do some light exercise. This is standard, first line therapy of lifestyle changes and sounds very reasonable. This compliant patient makes these changes and returns in two months, shocked and disappointed that his symptoms have become worse! Now he is given a low dose ACE inhibitor coupled with a diuretic for his hypertension and placed on metformin and glyburide to help control hyperglycemia. The glyburide tells the pancreas to secrete even more insulin and he gains more weight. Insulin also “ramps up” the enzyme HMG-Co A reductase which basically tells the body to produce even more cholesterol.

Excess insulin also drives the kidneys to retain sodium and waste magnesium,
which is an essential element for insulin receptor sensitivity. Hypertension and insulin resistance worsen. Usually at this point (if not done sooner) a statin is added along with niacin and another oral hypoglycemic and we ‘start the march’ to insulin therapy. This is why many of these patients will find themselves on six to nine prescription drugs and this is the current “Standard of Care” for this syndrome.

Let Your Food Be Your Medicine
Let us now suppose that the above patient visited a Chiropractic physician first. This particular physician is skilled in the use of a ‘muscle sparing’ protein diet, not a hyper protein diet ala Atkins. This diet is also low in fat, particularly saturated fat and is very carbohydrate restrictive (providing about 40 grams of carbohydrates daily mainly from fibrous vegetables). The physician explains the “medical model” of Syndrome X and relates how the overproduction of insulin can contribute to all his symptoms.

Correcting hyperinsulinemia is very straightforward: all carbohydrates (with the exception of fiber) will eventually be turned into glucose….sometimes quickly, sometimes slowly. As the glucose is absorbed the pancreas begins to secrete insulin (in this case, too much insulin). By restricting the carbohydrates the production of insulin is immediately reduced. The patient is interested but confides that he can be hypoglycemic at times and is afraid of such a restrictive protocol. The physician relates that hypoglycemia is usually the consequence of an overproduction of insulin, not a lack of carbohydrates. He further explains the body has “three tanks of energy” from which to draw. Glycogen (or our stored glucose), muscle, which can be broken down via gluconeogenesis to supply glucose and fat (triglycerides) which can be turned into glucose (from the glycerol) and ketonic bodies which most of the cells In the body can use for fuel. But the body draws on these compartments in a very specific order. It will always use the glycogen first and only when ‘that tank’ is empty, will it then begin to simultaneously burn muscle and fat.

The physician tells the patient if he keeps “putting fuel in the glycogen tank”, he will never be able to access his fat reserves, thus the restriction of carbohydrates. He also says that we never want to lose muscle, thus the inclusion of the adequate amount of protein to replenish what is lost to gluconeogenesis. During the first three days of this protocol the patient may feel a little tired or weak (as the body depletes its glycogen) but once this is gone and the body ‘switches over to muscle and fat’, he will have plenty of energy and hypoglycemic episodes will be a thing of the past. His patient is interested but asks: “ketonic bodies”, does that mean ketosis…I thought that was bad?” Again the physician explains that ketoacidosis is bad and that is why a Type I diabetic would never be placed on this program. In this case ketosis just means ‘living off your reserves’ and is the reason human beings were able to survive times of famines. His concerns allayed, the patient begins the program.

Six weeks later the elated patient returns to his Chiropractor. He is thirty pounds lighter and says that his medical doctor told him his blood work was fantastic! In layman’s terms the physician tells him: “Well you have actually reset your pancreas, it no longer is pumping out too much insulin and now you can start to put fruits, grains and dairy back into your diet”. After this patient’s glycogen reserves were depleted and carbohydrates continued to be restricted, the body had to ensure proper blood glucose levels were maintained. Under these conditions the pancreas produces more glucagon (which raises blood sugar) and much less insulin (whose primary function is to lower blood sugar).

But there is more to glucagon than this primary function. Glucagon stimulates two adipocyte (fat cell) enzymes (HSL and ATGL) and inhibits a third (Lipoprotein lipase). The result is the release of trigylcerides from the fat cell (to be used a fuel) as opposed to insulin’s effect which is to store fat. Glucagon enhances the entry of free fatty acids across the mitochondrial membranes so they can be used as fuel (insulin inhibits this). Glucagon also greatly inhibits the action of HMG-CoA reductase (along with all the other enzymes necessary for cholesterol synthesis) and forces cells to pull cholesterol from the blood stream via ‘ramping-up’ LDL receptors (1983 Nobel Prize in Medicine). This is why this patient’s lipid panel came back stellar. Finally in the kidneys the retention of sodium (caused by excess insulin) has now been corrected and his hypertension has resolved. The pathophysiology of Syndrome X is predictable. The reversal of this syndrome is also predictable and repeatable! As a matter of fact this exact method is being employed by over 700 chiropractic practices in the United States and Canada as well as many medical practices. Tens of thousands of patients have experienced same benefits described here.