REVISITING DR. BEATRICE GOLOMB'S 2008 MAGNUM OPUS ON CHOLESTEROL & STATINS
THE MORE THINGS CHANGE, THE MORE THEY STAY THE SAME
"Statins are a widely used class of drug, and like all medications have potential for adverse effects (AEs). We hypothesize, and provide evidence, that the demonstrated mitochondrial mechanisms for muscle AEs have implications to other nonmuscle AEs in patients treated with statins. In meta-analyses of randomized controlled trials, muscle AEs are more frequent with statins than with placebo. A number of manifestations of muscle AEs have been reported, with rhabdomyolysis the most feared. AEs are dose dependent, and risk is amplified by drug interactions that functionally increase statin potency, often through inhibition of the cytochrome P450 system. An array of additional risk factors for statin AEs are those that amplify (or reflect) mitochondrial or metabolic vulnerability, such as metabolic syndrome factors, thyroid disease, and genetic mutations linked to mitochondrial dysfunction. Converging evidence and empirical considerations suggest that mitochondrial dysfunction may also underlie many non-muscle statin AEs... such as cognitive loss, neuropathy, pancreatic and hepatic dysfunction, and sexual dysfunction. Physician awareness of statin AEs is reportedly low even for the AEs most widely reported by patients."
When it comes to cholesterol, our government, in cahoots with both the medical community and BIG PHARMA, uses a constant stream of PUBLIC FEAR CAMPAIGNS geared at scaring you into wanting to lower your CHOLESTEROL. And not just to lower your cholesterol (there are plenty of natural ways for the average person to accomplish this), but to lower it via one of the most popular classes of drugs in America, STATINS. And here's the rub...
You'll never hear me say that statins don't lower cholesterol. The truth is, they frequently lower it like gangbusters. The problem is that there is often a massive price to pay for lowering cholesterol with statins, in what Dr. Golomb refers to as "AE's" (adverse events). Unfortunately, few people are aware of the hundreds of studies that have shown time and time again that AE's are reported to the proper authorities not much more than 1% of the time (HERE), making most medications appear much safer on paper than they are in the real world. I am going to use today's post to revisit Dr. Golomb's amazing study, because unfortunately, the more things have changed, the more they've stayed the same.
Lest we fail to grasp how important this study was, Dr. Golomb began by telling us that, "Statins have been the best selling prescription drug class in the US and include atorvastatin, the best-selling prescription drug in the world – indeed in history." While this is no longer completely accurate, it's largely so, with the #1 selling drug still from the statin family of drugs, Crestor (rosuvastatin) instead of Lipitor (atorvastatin). And because so many people are unnerved by the mere mention of the word cholesterol, Golomb provides and extremely basic lesson in cholesterol physiology, helping make those without medical training aware of the various functions it serves as well as the substances for which it's a precursor.
- SEX STEROIDS: ESTROGEN, PROGESTERONE, and TESTOSTERONE, just to name the more common ones, are made from cholesterol.
- CORTICOSTEROIDS: Corticosteroids, glucocorticoids, mineralocorticoids, and others (cortisone, cortisol, aldosterone, etc) are of critical importance for a wide variety of physiological functions.
- BILE ACIDS: Bile (gall) is an important digestive juice that's made by your liver and stored in your gallbladder. PROPER DIGESTION is compromised without it.
- VITAMIN D: How cool is it that sunshine turns cholesterol into one of the most important vitamins in your body --- Vitamin D! Just understand that Vitamin D is not really a vitamin as much as it is a hormone / hormone precursor, with about a jillion important functions.
- LIPID BI-LAYER: Every single cell in your body is contained within a LIPID BI-LAYER made up largely of cholesterol.
So, as you can see, cholesterol has a lot of important functions. Knowing what these are allows us to start figuring out what sort of AE's a person might have if they deplete their cholesterol or attack the metabolic pathways that either manufacture or utilize cholesterol. We'll get to that, but first I want to talk about the why of this study --- why are statins such a problem for so many people? Dr. Golomb sums it up in a single sentence. "Statins lead to dose-dependent reductions in coenzyme Q10, a key mitochondrial antioxidant and electron transport carrier that serves to help bypass existing mitochondrial respiratory chain defects." Allow me to explain.
MITOCHONDRIA are the organelles within each cell that manufacture cellular energy in the form of something called ATP. Every single function of the body requires ATP, and all of the body's numerous chemical reactions (including those that make ATP) are catalyzed by enzymes --- substances that speed the reaction up, in many cases thousands of times faster than would occur without the enzyme. Co-enzyme Q10 is one such critical enzyme. What Dr. Golomb is saying is that if you don't have enough CoQ10 to act as a catalyst, not only will you not be able to keep up with your body's massive demands for cellular energy, but you won't be able to bypass any existing "MITOCHONDRIAL RESPIRATORY CHAIN DEFECTS" in a "dose-dependent" fashion. In other words, the higher the daily dose of statins or the longer you've been on them, the greater the chance you have of developing some really nasty health problems. If you want to see what these look like, click the link and take a look at the pie graph.
As many people are aware, far and away the most common side effects of statins involve muscle. "The best recognized and most commonly reported AEs of statins are muscle AEs, and include muscle pain, fatigue and weakness as well as rhabdomyolysis." Most people understand the first group of AE's mentioned, but if you aren't quite sure about RHABDOMYOLYSIS and its relationship to the others, be sure and click the link because Rhabdo is freaky stuff!
Before I move on, I need to talk about a phenomenon seen with almost all drugs, but greatly exaggerated with statins; the ability to be on both the good and bad side of the equation as far as the effects of the medication are concerned. Allow me to explain. There are numerous studies that show varying amounts of benefit to certain physiological functions with statins. The example Dr. Golomb used was "improved walking distance". However, in similar fashion to a bell curve (in this case the bell will be somewhat lopsided), some studies show as many people having problems (AE's) as people being helped. This is because statins tend to have strong effects either way, positive or negative, and in some cases, both, simultaneously. For instance, a person taking a statin might be able to walk further without pain, but with every dose is increasing their chances of developing statin-induced AE's. So, although the gross effect of Dr. G's analysis was that statins don't cause muscle pain, she believes it was because the AE's were balanced out by significant numbers of people who improved on the drugs.
"Evidence supports the proposition that antioxidant effects of statins underlie (or contribute to) many fundamental statin benefits – including benefits to flow and oxygen delivery and inflammation. These effects may participate in improved walking distance in patients on statins, including benefits to muscle/walking in persons with and without peripheral artery disease. Yet a subset of people reproducibly exhibit increases in markers of oxidation on statins, and the occurrence of this increase has been tied to muscle pain while on statins."
As noted by Golomb and her team, statin-induced muscle problems unfortunately do not always resolve once people stop taking them (be sure to read the comment from Chris Wunsch in my post on Rhabdo above). "Muscle effects arising on statins do not uniformly resolve fully with statin discontinuation." In some cases, these effects are described as only "partially reversible." And of these, she describes Rhabdo as "among the best-recognized and most feared complications of statins; it occurs when muscle damage is severe, leading to a marked elevation of CK (e.g. in excess of 10 times the upper limit of normal) often accompanied by evidence of renal dysfunction and occasionally renal failure and death." The list of other problems directly associated with Rhabdo include severe malfunction of, "heart, pancreas, liver, bone marrow, respiratory function, and central nervous system toxicity" or, as this letter to the editors of the American Journal of Medicine (Multiorgan Failure Induced by Atorvastatin) by a group of three specialists indicated, "all of the above."
It was the crazy side effects that kept MY FATHER IN LAW from taking statins. Awesome guy who spent a chunk of a year in Jefferson Barracks polio hospital when he was seven --- iron lung and the whole bit. Despite the fact that he simply could not take statins because of muscle AE's (something especially problematic is someone with post-polio syndrome), his doctors would hound him on every single doctor visit. It seems that this is a common theme.
Dr. Golomb wrote, "Although some investigators promote very low LDL cholesterol targets, proposing that lower is better and no LDL-C is too low, the US FDA has stated that 'all statins… should be prescribed at the lowest dose that achieves the goals of therapy (e.g. target LDL-C level).' Intensive statin treatment in RCTs does not improve mortality, even in patients with heart disease, relative to less intensive treatment. Moreover, intensive treatment comes at the cost of an increased risk of adverse outcomes." I once had a very young, thin, and at least apparently healthy patient, whom I quizzed as to why he had written on his intake forms that he was on statins. He replied that since his father had previously suffered a heart attack, his doctor suggested that he should go on statins in order to prophylactically prevent one of his own, especially since he had 'good insurance'. No lie, his total cholesterol was under 100 --- the physician's target level. Gulp!
We know that statins cause muscle side effects, but what about other side effects? "Drug interactions arise when drugs inhibit metabolic pathways of statins, compete for metabolism with statins, or cause similar or interacting toxicity. Several widely used statins – atorvastatin, simvastatin, and lovastatin are metabolized by the cytochrome P450 pathway." I've written extensively about BIOTRANSFORMATION, and the body's need to be able to clear toxins (not to mention DRUGS) via the P-450 CYTOCHROME SYSTEM. If you cannot clear drugs (statins included) from your system, they build up and cause problems. What sorts of problems? They affect the body's 'powerhouse,' the mitochondria.
"While a medley of potential mechanisms may cause or contribute to statin AEs, mitochondrial mechanisms have been repeatedly implicated in muscle AEs. Mitochondrial defects predispose to problems on statins. Additionally, statins predispose to mitochondrial defects in all users and, to a greater degree, in [EPIGENETICALLY] vulnerable individuals. Dose-dependent reductions in coenzyme Q10 can reduce cell energy, promote oxidation, promote apoptosis [cell death], and unmask silent mitochondrial defects."
Although the most common AE's are muscle-related, there are plenty of others. Listen as Golomb explains. "Muscle and brain are the organs most classically affected in mitochondrial disease (mitochondrial myopathy and encephalomyopathy are classical manifestations of respiratory chain diseases). Muscle is highly aerobically dependent and selectively vulnerable to mitochondrial pathology. But given the evidence for mitochondrial vulnerability and pathology related to statin AEs, it merits note that other organs – including brain, liver, heart and kidney – can be affected by mitochondrial pathology as well, and we suggest mitochondrial mechanisms may also be involved in a range of nonmuscle statin AEs." Without spending inordinate amounts of time on each one, what are these AE's? In no particular order they include, "mitochondrial encephalomyopathy, fatigue, cognitive problems, gastrointestinal and neurological symptoms, psychiatric symptoms, sleep problems, and glucose elevations." All of this begs the question, what can be done to reverse course and get better?
"Randomized trial evidence has little to offer in understanding recovery profiles for statin AEs. Even for the most commonly reported AEs involving statins, patients state that physicians often dismiss the possibility that their AE may be statin related. Failure to recognize drug AEs can prevent needed reassessment of the risk-benefit profile for statin treatment – and where appropriate, modification of the treatment regimen, in the face of possible or probable statin AEs."
This is exactly what I saw with my father in law. No matter how serious the side effects or how many times he told his doctors he could not take statins because they caused both pain and weakness, they constantly pushed him to take the drugs. "Try them again, you might have gotten over your reaction to them. It may have been a fluke. Try a different dose. Try a different drug. Try that drug with this drug." It was crazy. And although the first step in solving AE's of all sorts should probably include supplementing with CoQ10 (as well as calling your doctor to be taken off the statin immediately), there are plenty of others that could make a difference as well. Chief among those would be diet, which was not mentioned in this meta-analysis, although Dr. Golomb has lectured on EVIDENCE-BASED DIET.
As you've seen, cholesterol is important. It's good stuff. Good stuff. So, why does it sometimes stick to arteries? When the body is in A STATE OF PERPETUAL INFLAMMATION, the arterial walls become damaged and in similar fashion to other epithelial tissue barriers, "LEAKY". The body then uses the wax-like fat, cholesterol, to patch the damage. This process is also dose-dependant, meaning that the more SYSTEMIC INFLAMMATION, the greater the damage that must be repaired, and the more cholesterol is ultimately deposited on the arterial walls. And what does society continue doing (medical community included)? The public is continually told, bad cholesterol, bad cholesterol, bad cholesterol, good statins, good statins, good statins. And through all of this, there's another dirty little secret that I haven't even mentioned yet.
In similar fashion to our national war on BLOOD SUGAR (via gravy-sucking DIABETES DRUGS), we continue to viciously attack surrogate markers (in the case of statins, cholesterol), while the real markers of health (rates of morbidity and mortality) barely budge --- the whole relative risk -vs- absolute risk phenomenon (HERE). In other words, even though statins frequently lower cholesterol like crazy, they have far less effect on improving your chances of having heart attacks, strokes, or an early death. And let's be honest with each other for just a moment; who can trust our current cholesterol guidelines anyway (HERE)?
Just like the FLU VACCINE, which I have been spending a great deal of time on recently, statin drugs don't really do what's claimed of them. Fortunately, however, if you have issues with cholesterol, there are ways to attack the inflammation that is at the very least, a significant contributing factor (HERE). And as always, be sure and ask your doctor if it's safe to switch from a diet of TWINKIES and HYPER-PROCESSED GRAINS, to a diet of WHOLE FOODS, based on ANTI-INFLAMMATORY PROPERTIES (I've been a fan of those under the PALEO umbrella for a long time, although KETOGENIC is exciting for helping regulate cholesterol as well). Dr. Golomb's ground-breaking study is one more proof that your doctor can't do it for you; that real health is largely on your shoulders.