The debate about the safety of statins continues to rage, with some researchers claiming that they are essentially no more harmful that placebo. In reality, though, the evidence on which these claims are based is flawed for several reasons. Here are just some of those reasons:
1. Commercial sponsors of clinical trials may not be motivated to search exhaustively for potential side effects..
2. Many trials do not state clearly how and how often adverse effects were assessed. Because of this, it far from certain that all adverse events have been recognised and logged appropriately.
3. Trial volunteers tend to be enthusiastic individuals, and may therefore be less likely to report side effects than patients in routine clinical practice.
4. Many trials have a ‘run-in’ period where individuals are given a placebo to help ensure adequate compliance with medication. This can cause studies to be ‘enriched’ with highly motivated individuals who, again, may be less likely to complain of side-effects.
5. One major statin trial (The Heart Protection Study) employed a run-in period which subjected all potential participants to the active drug. Individuals with evidence of adverse events were excluded, which obviously means a higher percentage of ‘statin tolerant’ individuals made it into the study proper.
6. Several studies are of short duration and, worse still, may have been subject to early termination (something which tends to downplay harm and exaggerate benefits).
7. In many trials, adverse effects are only deemed to have occurred if there’s been extreme deviation from normal biochemistry (for example, judging that myopathy has occurred only when creatinine kinase levels are 10 times the upper limit of normal or higher). Setting the bar this high obviously works to depress side effect rates.
8. Many studies exclude types of individuals who exist in the real world and may take statins, including older patients, patients with other conditions or on other drugs that may make them uniquely sensitive to adverse effects from statins.
9. Published accounts of clinical trials in medical journals generally report only a minority of adverse events compared to full ‘clinical study reports’.
Plus, it should be borne in mind that statins reduce cholesterol by inhibiting an enzyme in the liver known as ‘HMG-CoA reductase’. This enzyme ‘drives’ cholesterol production but it also facilitates the production of a substance known as ‘coenzyme Q10’ – an essential player in the production of what is known as ‘adenosine triphosphate’ (ATP) – the most basic unit of energy ‘fuel’ in the body. We know that giving statins to people does indeed have the capacity to lower levels of CoQ10 in the body [1].
Depletion of CoQ10 is thought to be a major reason for why statins can reduce energy production (and therefore provoke fatigue) in muscles. However, it’s worth bearing in mind that the heart is a muscle, and depleting it of CoQ10 may be hazardous for cardiac health. Specifically, it may weaken the heart and lead to what is known as ‘heart failure’. Previously, researchers have noted the ability for statins to induce CoQ10 depletion in both humans and animals [2]. In this particular review, the authors concluded that:
Statin-induced CoQ10 deficiency is completely preventable with supplemental CoQ10 with no adverse impact on the cholesterol lowering or anti-inflammatory properties of the statin drugs. We are currently in the midst of a congestive heart failure epidemic in the United States, the cause or causes of which are unclear. As physicians, it is our duty to be absolutely certain that we are not inadvertently doing harm to our patients by creating a wide-spread deficiency of a nutrient critically important for normal heart function.
In a recent study, the effect of supplementing individuals with CoQ10 was tested in a group of individuals who were also given statins [3]. In this study, 62 individuals with heart failure were put on one of two regimes for 4 months.
1. a statin (atorvastatin 10 mg a day) plus 100 mg of CoQ10, twice a day
2. a statin (atorvastatin 10 mg a day) plus placebo, taken twice a day
The individuals in the study were subjected to a range of measurements including the heart’s ‘ejection fraction’ (basically, how much blood the heart pumps with each beat), and levels of the substance ‘N-terminal B-type natriuretic peptide’ (higher levels are generally found in worsened heart function). Compared to the placebo group, those taking CoQ10 were found to have better ejection fractions and lower levels of N-terminal B-type natriuretic peptide.
My conclusion, that CoQ10 depletion is a genuine potential issue in those who take statins, and that CoQ10 supplementation should at least be considered by those who take statins or have taken them (particularly if they suffer from heart failure or other symptoms linked to CoQ10 depletion).
References:
1. Passi S, et al. Statins lower plasma and lymphocyte ubiquinol/ubiquinone without affecting other antioxidants and PUFA. Biofactors 2003;18(1-4):113-24
2. Langsjoen PH, et al. The clinical use of HMG CoA-reductase inhibitors and the associated depletion of coenzyme Q10. A review of animal and human publications. Biofactors 2003;18(1-4):101-11
3. Pourmoghaddas M, et al. Combination of atorvastatin/coenzyme Q10 as adjunctive treatment in congestive heart failure: A double-blind randomized placebo-controlled clinical trial. ARYA Atheroscler. 2014;10(1):1-5
Always worth reminding people of the cynical behaviour of the Big Pharmaceutical Companies.
“The pharmaceutical company, Merck, was issued a patent (4,933,165) on a special medication combining a statin medication and Co-Enzyme Q10.
The researchers knew back in the late 80s and early 90s the significance of adding Co-Enzyme Q10 to statins. Furthermore they knew very well the negative impact of taking statins without supplementing with CoEnzyme Q10.”
From ww.functionalmedicineuniversity.com/public/784.cfm amongst many other sources of this info.
And they helpfully link to the patent at http://www.functionalmedicineuniversity.com/statin-CoQ10.pdf
From Chapter 1, How Statin Drugs Work, of the book by Dr Duane Graveline, ‘The Statin Damage Crisis’ (2009):
“.. .. glucose is converted into the two-carbon molecule […] known as acetyl-CoA.”
These simple fragments then venture along the biosynthetic pathway from which cholesterol is produced.
“Next, three molecules of Acetyl-CoA combine stepwise to form the six-carbon hydroxymethyl glutaric acid part of the complex known as HMG-CoA”
Aha, so HMG-CoA stands for ‘hydroxymethyl glutaric acid’.
Then, under the influence of an enzyme nature evolved especially for this important task, two molecules of HMG-CoA are melded together to form mevalonic acid. The enzyme is called HMG-CoA reductase.
Statins interfere with way this enzyme acts, thus reducing the amount of mevalonic acid that can be synthesised, into cholesterol, CoQ10, and a band of four other important biochemicals.
Now I do not ‘know’ this to be the case, but reason and logic does strongly affirm that mevalonic acid is an important molecule within biology and evolution.
I think the logic is as this; that if a species has blood and is inclined to eat a meal of food, as opposed to photosynthesising food for itself, then it has very real need of mevalonic acid, and the cholesterol that is then fashioned from mevalonic acid a step or two down the pathway.
In recognition of the great evolutionary step forwards represented by the emergence of this pathway, termed the acetyl and mevalonate pathway, Dr Graveline directs it may be about 3.5 billion years old. Mevalonic acid and cholesterol come with some ‘provenance’ then. In the broadest of terms the diversity of species would be restricted to plants mostly, without this significant advance in biochemistry, and there would be no blooded species to speak of, and not least because speech could not arise in humans without cholesterol.
Since cholesterol is a big feature of the synapses of the brain the kind of intelligence evident in the human species simply would not be possible without cholesterol. One has to despair, I think, or in the very least I cannot help but feel despair that members of human kind think it intelligent to wage war upon the very biochemical, and the very important pathway behind it, that permitted not only the evolution of ‘sophisticated’ blooded species like us, but all the ancestral species from the moment in evolution when blood became a possibility. We humans are so sophisticated we wage war on the biochemical and pathway that can account, as part of a suite of things, for the level of intelligence we possess. And if that ain’t dumb, then I don’t know what is.
* * *
Incidentally, certain oxidised cholesterols (not cholesterol itself) can convey oxidative stress to certain cells in arterial tissues and initiate the growth of fatty plaques, and it also appears homocysteine can do much the same. But here it gets really intriguing.
Some cholesterol oxides result from auto-oxidation, but there are many more that are produced enzymatically. As with the enzyme HMG-CoA reductase the involvement of enzymes suggests that the process has some evolutionary advantage. Cholesterol oxides that result from the involvement of an enzyme very likely has some positive contribution to make. So, there are certain cholesterol oxides that have been proven to be atherogenic, and these fall within the group that can arise upon contact with oxidising agents (such as ‘air’ – ‘auto-oxidation’), while more than forty possible and enzymatically arising cholesterol oxides might not be so bad after all.
When cholesterol was fed to rabbits, chickens, rats and squirrel monkeys the deleterious effects were actually down to cholesterol impurities. Sadly this detail escaped the attention of Dr Ancel Keys who fashioned the (false) fat/cholesterol hypothesis. (Really, not much was known about cholesterol impurities until after Keys fashioned his hypothesis.)
The most toxic impurities in cholesterol samples have been identified as oxides of cholesterol, with cholestane-3B,5a,6B-triol and 25-hydroxycholesterol (25-HC) being the principal biologic toxins.
Now, 25-HC can become sulfated (sulfur is added) and then it becomes 25-hydroxyl cholesterol sulphate (25-HC3S). The properties of 25-HC and 25-HC3S are in sense diametrically opposed. According to Stephanie Seneff, PhD., “Whereas 25-HC present in the medium causes the macrophages (a certain cell type) to synthesise and store cholesterol and fatty acids, 25-HC3S […] promotes release of cholesterol and causes fat stores to shrink.” 25-HC could lead to apoptosis and cell death (as demonstrated in vitro), whereas 25-HC3S did not. Seneff has postulated that the sulfated cholesterol oxygen radical (25-HC3S) is essential to the process of conveying cholesterol and oxygen to the heart muscle.
Garlic, onions, turmeric, and egg yokes, along with other sources of sulfur, might be good for you through, amongst several eventualities, facilitating conversion of 25-HC to 25-HC3S. Certainly sulfur takes the sting out of one toxic cholesterol oxide.
Dr Briffa, here’s a twist I know will intrigue; amongst the several possible cholesterol oxides there is at least one that can act as as HMG-CoA reductase inhibitor (!!?), as my source has it [Biological Effects of Cholesterol Oxides; Peng & Morin (1992)]. I feel the need to read into that and fill any gaps in the intervening years.
To expand a little:
Stephanie Seneff also considers that the sulphation (sulfation?) may occur in plaques that form (exclusively) in arteries feeding the heart.
“The macrophages in the plaque take up LDL, the small dense LDL particles that have been damaged by sugar… The liver cannot take them back because the receptor can’t receive them, because they are gummed with sugar basically. So they’re stuck floating in your body… Those macrophages in the plaque do a heroic job in taking that gummed up LDL out of the blood circulation, carefully extracting the cholesterol from it to save it – the cholesterol is important – and then exporting the cholesterol into HDL – HDL A1 in particular… That’s the good guy, HDL.
The platelets in the plaque take in HDL A1 cholesterol and they won’t take anything else… They take in sulfate, and they produce cholesterol sulfate in the plaque.
The sulfate actually comes from homocysteine. Elevated homocysteine is another risk factor for heart disease. Homocysteine is a source of sulfate. It also involves hemoglobin. You have to consume energy to produce a sulfate from homocysteine, and the red blood cells actually supply the ATP to the plaque.
So everything is there and the intent is to produce cholesterol sulfate and it’s done in the arteries feeding the heart, because it’s the heart that needs the cholesterol sulfate. If [cholesterol sulfate is not produced]… you end up with heart failure.”
Going on to say;
“So, 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.”
So statins may be causing heart failure in more than one way.
Yes, Steph Seneff considers sulphur central to conveyance of energy (electron transport0 in metabolism because of the range of oxidative states it can occupy.
Seneff is quite radical in her thinking which determines that those who choose to seek out the merit in what she directs must attempt to follow and verify her premises. Only lately have I taken up with interest in her work — and there is much to get up to speed with.
Another of the interesting things she directs is that cholesterol sulphate is the likely substrate for vitamin D3 sulphate (D3S) which is synthesised by the action of the sun falling on skin. Synthesis of D3S mimics the conversion of cholesterol to regular vitamin D3.
However, where D3 is fat soluble and must hitch a ride within lipoproteins, one might consider, D3S is water soluble. D3S then, compared to D3, is the form most likely to be found freely circulating in blood. Both forms of vitamin D3 may be healthful on account of their antioxidant properties, but through being water soluble the sulphated form of vitamin D3 affords possibilities fat soluble regular vitamin D3 alone cannot fulfil.
If there ain’t enough fat and sulphur in the diet, and if you don’t get enough regular exposure to sunlight, a person could be missing out upon an important antioxidant — the sulphated version of vitamin D3.
Seneff could well be right about the significance of the potential energy states attached to sulphur, because if life isn’t a quantum effect of some kind I’d be hard pressed to explain what ‘life’ is.
Anyway, we have been brainwashed into thinking cholesterol is bad, and that is not the case. Cholesterol does not feed into the advance of cardiovascular disease, but there are real reasons to think that certain cholesterol oxides and/or homocysteine, acting jointly or severally, do.
When I was first prescribed statins years ago, I suffered quite bad muscle weakness in my hands – I was unable to grip my tennis racket to the extent that it would turn in my hand when taking a shot. In addition, I noticed when in bed, that my heart, heard in my ear on the pillow had begun to go “shlurp shlurp” instead of the nice strong “lib dub”. I didn’t like that at all and it frightened me somewhat.
Quite by chance I read in John Briffa’s column in The Observer about the importance of supplementing with Co-enzyme Q10 when taking statins. This I did and after a few weeks all was restored to normal.
Now, my friend and neighbour who has a long history of heart problems and takes warfarin, has become more ill with an enlarged heart. I told her about Q10 and she said she would ask her doctor about it. Her doctor has told her that on no account should she supplement with Q10 because it will thin her blood too much. Can this be right? I find it hard to believe that a naturally occurring enzyme within the body should have such a side effect.
Please advise, one of you clever people out there. It saddens me that my friend is slowing dying with heart failure when a popped pill could transform her life.
Needless to say I stopped taking statins some time ago and have not looked back.
Thank you for all your good advice, Dr Briffa – Q10 and magnesium for muscle cramp though that turned out eventually to be caused largely by the beastly statin.