Statin doctors were quick to discount the findings. But aren't statins supposed to stop atherosclerosis? In this case, whether or not the statins caused the problem, they certainly didn't prevent it.
Is there a mechanism whereby statins may increase calcium deposits in arteries?
Let's look first at another side effect of statins; "certain cognitive effects such as memory loss and confusion".
Is there one effect of statins that could account for both these results?
Statins are HMG-CoA reductase inhibitors. HMG-CoA reductase is the rate-limiting enzyme for cholesterol synthesis. Cholesterol, like most lipophilic hormones and vitamins, is a terpene derivative, or isoprenoid.
Some of the essential isoprenoid structures, such as those found in vitamins E and A, are formed in plants, but others, including Co-enzyme Q10 (ubiqionone) are formed in the cytosol from a product of the HMG-CoA reductase pathway, mevalonate.
That statins can lower ubiquinone levels is well-known and accounts for occasional serious adverse reactions.
However, ubiquinone and cholesterol are not the only HMG-CoA reductase dependent compounds essential for health.
the repeating isoprene group derived via HMG-CoA reductase is bracketed.
Vitamin K is present in green vegetables and vegetable oils as phyloquinone, and in fatty animal foods as menaquinone-4 (MK4), while bacteria produce menaquinone-7 (MK7).
Vitamin K1 is converted to vitamin K2 by removal of the phytyl side-chain and replacement with an isoprenoid side-chain.
When this occurs in the brain the MK4 produced is an essential co-enzyme for the synthesis of special sulfur-containing lipids called sulfatides. Low CNS sulfatide levels are associated with congnitive decline and seen in the early stages of Alzheimer's disease.
Low sulfatide content in brain myelin has been recently linked with the disruption of myelin integrity [14, 21], whereas the disruption of myelin integrity was implicated as an essential contributor to cognitive deficit [6, 7, 43, 44]. Although our findings of dietary-associated decreases in myelin sulfatides suggest a potential disruption in myelin integrity in evaluated brain regions, it is currently unknown whether such disruption would be sufficient to modify motor and cognitive functions controlled by these brain regions.
In the present study both dietary forms of vitamin K1 were converted to menaquinone-4 (MK-4) in the brain.
Doug Bremner states that congnitive impairment is more commonly reported with the more lipid-soluble statins, such as Zocor (simvastatin) and Lipitor (atorvastatin), which cross the blood-brain barrier, and is rarer (but still seen) with water-soluble statins such as Pravachol (pravastatin).
Vitamin K2 as menaquinone-4 (MK4) also prevents arterial calcification.
Warfarin-treated rats were fed diets containing K1, MK-4, or both. Both K1 and MK-4 are cofactors for the endoplasmic reticulum enzyme γ-glutamyl carboxylase but have a structurally different aliphatic side chain. Despite their similar in vitro cofactor activity we show that MK-4 and not K1 inhibits warfarin-induced arterial calcification.
Chris Masterjohn has long been writing about the importance of vitamin K2 on his blog at Weston A. Price.
Thus there may be a common mechanism for both calcification and memory loss; decreased conversion of vitamin K1 to MK4.
Now it may be that a diet high in animal fat and fermented dairy products will supply all the MK4 you need. But is a person being prescribed statins to lower cholesterol going to be advised to consume such a diet?
Only if the doctor knows that the saturated fat lipid hypothesis is nonsense (the sugar-and-starch lipid hypothesis is another matter entirely).
An article postulating that statins might affect bone density by lowering K2 synthesis was published by Linda L. Demer in the journal Arteriosclerosis, Thrombosis, and Vascular Biology in 2001.
And now, eureka:
Vitamin K2 Is a Mitochondrial Electron Carrier That Rescues Pink1 Deficiency. Science (New York, N.Y.) 336(6086): 1306–1310. http://www.ncbi.nlm.nih.gov/pubmed/22582012
Still unknown if this happens in animals. Generally the amounts of K2 in mammalian mitochondria are considered to be too small to be have a functional role. But watch this space...
and here we have another quinone, PQQ, relatively recently discovered and present in tiny amounts, throwing its weight around:
Ofc it happens.
Here is one clue.
Mehta, Dilip S., Anselm De Souza, Ashok B. Vaidya, et al. 2010Method of Use of Vitamin K as Energy Enhancer in Diverse Disease States. http://www.google.com/patents?id=ucYdAgAAEBAJ, accessed August 5, 2012.
The studies you referenced regarding the conversion of vitamin K1 to mk4 in the brain were all done with rats.
Rats that have been fed only vitamin K1 have high levels of vitamin of vitamin K2 indicating that they readily convert K1 to K2. The conversion of K1 to K2 in humans appears to be negligible except in breast tissue so humans must get vitamin K2 ready made.
Both mk4 and mk7 forms of vitamin K2 will activate osteocalcin, the vitamin K dependent protein that is required for putting calcium where it belongs in teeth an bones, and will also activate MGP (matrix GLA protien) which is a potent inhibitor of vascular calcification (for which "there is no known alternative.
Surely if it was true that humans cannot convert K1 to K2, any vegans who don't eat fermented food would die from deficiency diseases.
It may indeed be true that low sulfatides play a role in Vegan Unfiltered Belief Syndrome.
Proof that humans convert K1 to K2 is the use of menadione (K3) in medicine to correct deficiency. This requires the addition of the isoprenoid side chain to form MK4, just as in the conversion of phytoquinone.
A negligible conversion of K1 may yet be good enough, if the diet is rich in it, but it does seem to decline with age and disease (just as ubiqinone synthesis does) so that animal foods may become more important as we age.
I think it likely that K2 can perform or supplement role of ubiquinone, but this has not been detected in animals yet.
The patent is highly speculative and, like most patents these days, pre-emptive.
They are extrapolating from the redox cycling, superoxide generating effects of menadione (which are more likely to produce cytotoxic effects, including hepatoxicity and apoptosis of cancer, than increase energy).
Whether boosting superoxide is good for you depends on three things; location, location, location.
The lack of effect of vitamin K1 on vascular calcification was shown in the Rotterdam study in which dietary intake by 4800 men and women of vitamin K1 and vitamin K2 was determined by food frequency questionnaires. During the 8 year follow up period the incidence of severe calcification of the aorta and the incidence of CHD mortality was 250% higher among the lowest tertile of vitamin K2 intake compared to the highest tertile. VITAMIN K1 INTAKE WAS NOT RELATED TO ANY OUTCOME.
It was noted that when vitamin K1 is absorbed in the gut, it is transported mainly to the liver by triglycerides while vitamin k2 is transported mainly by LDL to non-hepatic tissues. This perhaps partly explains the minimal effect of vitamin K1 on carboxylation of vitamin K dependent proteins. Chris Masterjohn's article in the Weston price Journal also noted that absorption of dietary vitamin K1 is insufficient to provide carboxylation of osteocalcin.
Here is my theory concerning the increased vascular calcification by statin users. Vitamin K2 is required for activation of MGP which is "the only known inhibitor of vascular calcification. Vitamin K2 is a fat soluble vitamin that comes primarily from animal fats in the western diet. About half of dietary vitamin k2 in the western world comes from aged cheese, 20% from other dairy products and most of the rest from meat and eggs.
Government dietary guidelines recommend limiting cheese consumption to one 1.5 ounce serving per week, consuming low fat or skim milk, limiting egg consumption, substituting vegetable spread for butter and reducing intake of meat fat, thereby assuring severe vitamin K2 deficiency in those who follow the guidelines. Doctors promote the low fat folly which is the cause of vitamin k2 deficiency which leads to vascular calcification.
That seems reasonable.
Low-fat will also affect K1 absorption.
I don't think K1 lacks the ability to provide benefit, just, as with carotenes, the benefit is highly dependent on good liver function, micronutrient status, and so on.
I don't think these effects of statins relate soley to cholesterol.
I think the extra vitamin effect of dietary K2 in the studies is superimposed on a baseline effect of K1 conversion to K2 which is not significantly affected by supplements.
Otherwise absolute risk of non-consumption of K2 would be absolute.
The protective effect of K1 conversion is small but more-or-less adequate for a great many people until statins or low fat-diet or antibiotics or some other factor disrupts it.
This is probably state-of-the-art on K2 biosynthesis:
the Rotterdam study only included elderly men and women (>55), the prospect study women 49-70.
K1 conversion can be expected to decline with age as ubiqinone synthesis does.
Also, in Prospect study it was the long-chain MKs; MK7, MK8, MK9, rather than M4, that showed benefit - OR, the foods supplying these (which would also contain other factors).
"Surely if it was true that humans cannot convert K1 to K2, any vegans who don't eat fermented food would die from deficiency diseases."
Some studies suggest that vitamin K1 can carboxylate vitamin K dependent (VDK) proteins such as osteocalcin but the capacity to do so is limited because of the limited absorption of K1 and the fact that most of the K1 is carried by TG to the liver, while most of vitamin K2 is carried throughout the body by LDL.
While vegans may get not die of vitamin K2 deficiency because either (a) vitamin K1 activates enough VKD proteins, or (b) sufficient K1 is converted to K2 to keep them alive, the adverse effects of K2 deficiency are quite severe. In the Heidelberg studies it was found that those in the lowest quartile of K2 intake, mostly mk7 from cheese, had a 300% increased risk of lung cancer mortality and a similar risk increase in risk of advanced prostate cancer. INTAKE OF VITAMIN K1 HAD NO EFFECT ON EITHER OUTCOME. Apparently conversion of K1 to K2 in those consuming gobs of veggies was not sufficient to prevent lung or prostate cancer.
Sometime around 1980 I read a book by Pritikin and got hung up on the low fat diet for many years. In about five years my teeth went bad and I had some may caps that my dentist asked me if I was eating rocks. (Chris Masterjohn and Denise Minger both had similar experiences with bad teeth resulting from low fat diet.). I attribute the problem to vitamin K2 deficiency. None of us apparently had enough K1 conversion to keep our teeth healthy.
I eat three or four ounces of aged cheese a day as the main source of vitamin K2.
I don't think K1 lacks the ability to provide benefit, just, as with carotenes, the benefit is highly dependent on good liver function, micronutrient status, and so on.
No, I don't think so, the same goes for carotens. Recently it was shown that biological availability of beta caroten was over estimated. It first appeared 6 bc are needed for 1 retinol, then 12, now it looks more like 26-51. Similarly, vitamin K1 tops, I think, at 300mcg per day if you even can get that amount from industrial plants. Vitamin K2 from bacteria in the colon is still of questionable availability. It looks that you have to eat sh*t to get it - some animals get deficiency when they are prevented to practice coprophagy paralleled with dietary deficiency.
Furthemore, all this depends on other contest of your diet.
I take my K2 from yellow looking butters, 1-2 caps per day Now Foods D3+K2 supplement, dairy products. I drink my supplements with grinded black pepper in water before meal, with some oil (usually cod liver oil, coconut oil, palm oil, fish oil, hemp oil)
BTW, the fact that vegans don't die on K1 is beside the point. There multiple levels of existance.
I advise you to check out Triage theory of Ames.
Here is a reference
McCann, Joyce C, and Bruce N Ames. “Vitamin K, an Example of Triage Theory: Is Micronutrient Inadequacy Linked to Diseases of Aging?” The American Journal of Clinical Nutrition 90, no. 4 (October 2009): 889–907. http://www.ncbi.nlm.nih.gov/pubmed/19692494.
George, The link you posted to the article by Kimie Nakagawa, "new Developments in Research on Vitamin K biosynthesis" was most informative.
Of particular interest was the lin between vitamin K and geranylgeranylpyrophospate (GGPP) which is one of the vital isoprenoids produced from mevalonate.
In the 1990s it was widely believed that statin-induced muscle dysfunction was due to depletion of CoQ10. A recent study attributes contractile dysfunction of skeletal muscles to GGPP depletion by statins which leads to contractile dysfunction due to reduced ATP in micro fibers with damaged mitochondria.(PMID 21127387: free full text) It is now apparent that CoQ10 is derived from GGPP.
Other adverse effects of statin induced GGPP deficiency include impairment of cell cycle progression and DNA synthesis (9425279), and neuron cell death that leads to neurodegeneration ((15030380 and 10751437)
Thanks for posting the most interesting article.
I think geranylgeranylation is essential for activating some proteins that are not quinone dependent.
The Rotterdam studies seemed to show no benefit from K1 or MK4. Only the MK7,8,9 effect was significant.
But this was not a clinical trial, the effect was of aged cheeses, and the results were attributed to MK7etc, but other factors were not ruled out.
The only reason I can see that MK7 would be more protective than MK4 is half-life. Unless only MK7 can have the mitochondrial function in animals...
Yes, I think Ames has the right idea.
Apes - gorillas and orangutans - must convert K1 and are close to us.
Carotene conversion depends on tocopherol status; vit E acts as midwife for vit A production.
Otherwise you get this:
Retinol also suppresses carotene conversion, so any study into conversion has to be done in low retinol state.
If a rat, which shares a common ancestor, converts K1 to K2 in the brain;
and vegetarian primates which are closely related to us and descended from the concestor still have those genes;
then the parsinimous hypothesis is that humans also have the ability, and that interference with conversion accounts for some of the side effects of statins.
Given that this will tend to occur when ubiquinone and cholesterol and protein geranylgeranylation are also likely to be sub-optimal.
As regards bad teeth on "healthy" food, I know what you mean.
However, consider that phytates and other antinutrients might also inhibit remineralisation, and that cheese has a locally protective effect on teeth, suppressing caries bacteria better than a toothbrush.
George, your comment about cheese being better than a toothbrush is most interesting.
Of course, the French tradition is to end a meal with a cheese platter rather than a sweet dessert - pretty obvious which one is better for unbrushed teeth!
Do you have any references for this?
On the MK4 v MK7 issue, I have read, I think from Chris Masterjohn, that the reason MK7 hangs around longer is that MK4 is absorbed more readily.
There is quote some debate about 4 v7, but I think its safe to say we won't go wrong getting both.
Interesting to note that the naturally occurring sources of K2 (except Natto) come packaged with animal fats, and a good dose of cholesterol and vit D.
A high statin, low fat diet sounds like a tailor made recipe for long term trouble!
_George, your comment about cheese being better than a toothbrush is most interesting._
Actually, there is more to this then K2. Vitamin C is called on weston price "invisible tootbrush":
Removing carbs is more effective then oral higyene any day:
Hujoel, P. “Dietary Carbohydrates and Dental-systemic Diseases.” Journal of Dental Research 88, no. 6 (June 2009): 490–502. http://thrivewithdiabetes.com/doc/Carbohydrates_and_diseases.pdf.
I strongly recommend reading Hujoel, because he is mainly right (apart from point where he writes bad about supplements using idiotic studies from Bjelakovic and friends, which itself is contradictive since he writes nice about Price who searched and found those food factors).
Apart from K2, Mg seems essential too.
There have been many studies about the caries inhibiting properties of cheese and many mechanisms have been proposed to explain these properties. In my opinion the vitamin K2 content of cheese plays an important part.
In "Nutrition and Physical Degeneration" Dr. Weston Price details clinical trials over a seventeen year period which found that a diet rich in vitamin K2 (activator X)
together with vitamin D3 and vitamin A from cod liver oil, healed dental caries and bone fractures and cured rickets.
The experiments by Dr. Price that found that vitamin K2 intake greatly reduced salivary bacteria levels and reduced carries incidence has received little attention. Dr. Price noted that "The addition of butter high in activator X to the diets of human beings suffering from tooth decay causes a marked change in the chemical constituents of the saliva and the growth of L. acidophilous." Before the change in nutrition, when tooth decay was considered active, L. acidophilous averaged 323,000 colonies per cubic centimeter of saliva, and, after treatment, averaged 15,000. These data are typical of many hundreds of clinical cases in which dental caries have been reduced apparently to zero."
Chris Masterjohn has discussed the findings by Dr. Price regarding the role of vitamin K in prevention of caries and noted that while it has been found that vitamin K2 exists in the second highest concentration in the salivary glands of all organs in the body, "to this day, no one has investigated the role of natural vitamin K in prevention of dental caries."
While no one has directly investigated the role of vitamin K in prevention of dental caries, there have been dozens of studies that have found that eating cheese, which is rich in vitamin K2, significantly reduces the incidence of dental caries.
According to a study by E.L. Herod (PMID 1877906) "The caries reducing properties of cheese have been the subject of intensive research. Most studies suggest that the use of cheese as the final food of a meal will help reduce caries" None of the studies reviewed have mentioned the high vitamin K2 content of cheese as a possible mechanism of caries prevention. The findings of a study from Umea University in Sweden (PMID 17167256), however, are consistent with the findings of Dr. Weston Price in that salivary bacteria level and incidence of caries were both found to be inversely associated with intake of vitamin K2 rich cheese.
The study from Umea, Sweden, evaluated the association between dental caries, saliva levels of bacteria and diet in children from infancy to four years of age. The study concluded that "Caries experience was negatively associated with the intake frequency of cheese (OR = 0.67) and positively associated with the salivary level of mutans streptococci (OR = 1.57). Caries experience was not associated with intake frequency or amounts of carbohydrate containing foods, with any other particular food, or with daily intake of energy, carbohydrate or any other macro or micro-nutrient". These findings solidly support the conclusion by Dr. Price that intake of vitamin K2 (activator X) reduces saliva bacteria levels, alters chemical composition of saliva, and reduces incidence of caries. It is reasonable to conclude that vitamin K2 is responsible for the "well established action of cheese in reducing dental caries."
Nice info, BUT, if they say that "intake frequency or amounts of carbohydrate" do not influence teeth, I can only shift delete that paper from my mind and nothing else. Ofcourse, they talk about association and kids typically eat high carb diet, so in that respect, the difference between 40% or 70% of carbs when teeth are in question is probably minimal. I am sure none of the kids was on low carb diet.
When microbiota is in qeuestion, K2 is growth factor for many bacteria in the mouth. In:
Reduction of vitamin K concentration by salivary Bifidobacterium strains and their possible nutritional competition with Porphyromonas gingivalis (http://goo.gl/MJebE) its concluded that bifidobacteria dentum sucesifully competes with p. ginvivalis for K2 and that creates more beneficial oral flora. This could be one mechanism. Other one could be that in absence of K2, Ca and Mg probably finish on wrong places (soft tissue) and people usually think that those minerals have homing device and know how to get to the teeth.
There is a third mechanism - better mitochondria function. CoQ10 is known to be beneficial and K2 is similar (or the same as) to Q10 in that respect. CoQ10 is known to help gingivitis and to be highly concentrated in saliva and to promote its secretion (http://goo.gl/n3nCB). As saliva is protective in every respect (http://goo.gl/4IoaT) this could be mechanism behind K2 too.
BTW, I found one study that looks at K3 and caries: http://goo.gl/MJubk
Now, this "oral probiotic" story is interesting and I wonder to what measure should you combine it with natural anti-biotics. Iodine for instance is awesome (no bacteria developed resistance) and recently it was shown that piper nigrum inhibits 75% of oral bacteria (see Fig 1). I recently started to use it when I have soar throat and it looks to help. Besides, as I already mentioned, it the most potent enhancer of biological availability known.
Forgot to put link to piper nigrum: http://goo.gl/a5Q3e
Very interesting discussion.
I found this on a BBC website: we have to factor in the short-chain fatty acids as modulating microbiota:
"Cheese protects against dental caries, partly because eating cheese causes more saliva to flow and neutralise acids, and partly because the cheese increases calcium concentration in the plaque stopping demineralisation. The fat in cheese also reduces the amount of bacteria on the surface of the teeth. So a small lump of cheese eaten after a meal or a sugary/acidic drink will help protect tooth enamel."
Odd-chain fatty acids seem to have largely unexplored benefits, as long as you have enough B12 to metabolize them.
But hang on; a protective effect of "fatty mouth feel"?
A supporting role of K2 in gum health, enhancing the effect of ubiqinone, is credible.
And also the possibility that milk products, being highly immunogenic foods, stimulate the release of saliva that is higher in immunoglobulins or lysozyme than usual. As the baby's immune system is undeveloped, milk contains factors that ensure it is less likely to be feeding the wrong troops?
Lactose is a poor sugar source for cariogenic bacteria; does galactose favour beneficial species?
"The anticaries effectiveness of galactose is dependent on its concentration: 5.0% galactose reduces the amount of caries on a high significance level, lowers the abrasion of the chewing surfaces, possibly because of the increased amount of serum calcium related to this galactose concentration, and diminishes the amount of film. 1.5% galactose prevents caries significantly and strongly reduces the amount of film; 0.5% galactose reduces the amount of caries non-significantly, but diminishes the amount of film. The effect is based on the property of galactose to occupy the receptors of the pellicle (layer of glycoprotein on the tooth enamel), hence the adherence of specific germs (for example, Streptococcus mutans) ceases in whole or in part."
There is not that much galactose left in cheese though. But what there is might be more sticky.
I suppose milk has really evolved to keep a toothless mouth healthy and support "milk tooth" growth.
Now surely competing for vit K would be only one of many ways in which bifidus suppresses gingivalis. Antimicrobial peptides being another.
Growth effect of menadione may relate to K1 which is a source of menadione; or to synthesis of vit K de novo by some bacteria.
Menadione has potent redox cycling and cytotoxic effects and the use of menadione may have exaggerated the effect of vit K.
The unknown vit K-like bifidus growth factor may have been PQQ.
Returning to the subject of statins: The term “HMG-Coa reductase inhibitors” is a widely used term for statins. However, according tothe studies of the Nobel prize winning scientist who developed statins, the drugs do not lower serum cholesterol by “inhibiting endogenous cholesterol synthesis” as is widely believed. Statins lower cholesterol by disabling existing reductase, an enzyme in cells that makes mevalonate , the source of “cell foods” (isoprenoids), including cholesterol, that are vital to cell function. Cells respond to statin deactivation of their source of nutrients by producing MORE reductase, and hence more cholesterol, to meet cellular needs. Simultaneously, cells increase the number of LDL receptors to provide a second source of nutrients. The increased LDL receptors move cholesterol from the bloodstream to cells thereby lowering serum cholesterol while stuffing cells with more cholesterol than they can metabolize. When scientists looked inside statin-treated cells they found crystals of the excess cholesterol.
The FDA initially approved statins trials for patients with defective LDL receptors (FH) who have high serum LDL cholesterol. Statins caused a 50% INCREASE in serum LDL in patients with 100% defective LDL receptors because the increased cholesterol synthesized by the liver can not be removed from the bloodstream by defective receptors. In patients with 50% defective receptors the increased number of LDL receptors triggered by the statin blockade of mevalonate lowered serum cholesterol.
The statin blockade of mevalonate deprives cells of isoprenoids vital to normal cell functions, including isopentenyl adenine that is required for DNA replication, CoQ10 which needed for cellular energy production and regeneration of anti-oxidants, and GGPP that is essential for prevention of neuro-degeneration and contractile dysfunction of skeletal muscles. Statins thereby cause many injuries including cognitive dysfunction, blindness, diabetes, muscle wasting, kidney failure, liver failure, heart failure and cancer.
Those with defective LDL receptors number only 1 in 500. Merck’s Nobel prize winning scientist Dr. Michael Brown greatly expanded the potential market for statins by convincing the FDA, without a shred of evidence, that most people with two normal LDL receptor genes and elevated LDL have “sluggish LDL receptors”.
The forgoing information on the mechanism by which statins lower cholesterol came from the recent book “How Statin Drugs Really Lower Cholesterol and kill you one cell at a time” by Hannah Yoseph, MD., and James B. Yoseph. Hundreds of excerpts of the scientific studies that were the basis of statin development are used to present overwhelming evidence that statins are toxic due to the deactivation of mevalonate, and that the increase in LDL receptors triggered by mevalonate deactivation of is the mechanism by which statins reduce serum LDL.
I think it not unlikely that low-dose or occasional use of some statins actually stimulates HMG-CoA reductase in some tissues.
There are rare conditions that would benefit from K2 suppression; metachromatic leukodystrophy and Krabbe's leukodystrophy, where sulfatides or their products accumulate, seem to be indicate a therapeutic role for Pravachol or Lipitor.
The increase in reductase is an automatic response by cells to statin toxicity in an effort to prevent cell death due to depletion of vital isoprenoids. Increased statin dosage requires a greater increase in reductase to prevent cell death in ALL tissues.
"In 1982, Brown and Goldstein used the reductase stimulating property of statins to make a line of mutant cells that produced 500 times the normal amount of reductase. These cells overcame cell death. Because cells made massive amounts of reductase, Brown and Goldstein were able to isolate a large enough sample to further their research on the elusive enzyme." (page 26)
"How Statin Drugs Really Lower Cholesterol" does a thorough job of presenting the information on just how statins work. When the authors get off the subject of statins they do poorly. The book has no index which is a pain.
It is puzzling to me that statins continue to be called "Reductase inhibitors" when they actually stimulate a significant increase in reductase production. I am surprised that none of the blogs have mentioned the book.
The article you mentioned on vitamin K and the triage theory was most interesting and led me to a more recent article on the same subject: (PMID 22489224). It seems that the vitamin K dependent (VDK) proteins related to coagulation are the most critical and those needs will be met first at the expense of less vital VDK proteins such as osteocalcin and Matrix Gla protein.
Fact; statins are natural. Well, some are, the rest are synthetic copies of a compound from traditional Chinese Medicine. (Oyster Mushroom - or Ping Gu)
It's natural, it's got to be good for you!
If your blood doesn't clot you die today, if your bones don't store Ca or your arteries do you may well die of something else first...
Triage theory fits with the thiamine hypothesis too, except that we have triage with the same enzyme (pyruvate dehydrogenase) used for 2 purposes, so the switching must be at gene expression level, probably PPARalpha activation.
"Fact: statins are natural.--It's natural, it's go to be good."
Not so. Just because statins are natural does not mean they are not toxic.
Fact: statins are derived from fungal toxins called mycotoxins (myco means "fungus".) In 1960 the term "mycotoxin" was coined after a fungal toxin in commercial nut feed was found to be the source of rapid and deadly cancer epidemics in farm-raised turkey and trout. The discovery spawned the "mycotoxin gold rush" for the next fifteen years as drug companies searched for more toxigenic agents from food molds.
Mycotoxins block growth and reproduction of competing organisms and are poisonous to microbes and human cells.Most mycotoxins come from four species of fungi: Aspergillus, Penicillium, Proteous and Monascus. These are the same four fungal species used to make statins.
Statins look like the precursor to mevalonate: reductase is "tricked" into bonding with the statin. Reductase in turn is disabled which causes single-celled organism to die quickly while multi-celled organism die one cell at time.
The scientists who developed statins worked for years trying to find a means to use statins to stimulate an increase in the number of LDL receptors to lower serum cholesterol without disabling the mevalonate pathway. They failed. They eventually realized that the disabling of reductase and stimulation of LDL receptors are hard wired to act together. What makes statins work also makes them toxic.
Or in Hep C you have a VLDL lowering effect from statins, which you would want to restrict the virus, but LDL-R upregulation, which is counterproductive...
so fluvastatin has some antiviral effect, but not consistent enough to become a standard treatment.
I'm wondering, if statins are so toxic, how many million of patients taking them seem to do fine. I've long been aware, and leery, of statins, but was finally convinced by my cardiologist to begin a 10mg dose of pravastatin. After two months all my lipids (including HDL, unfortunately) are much lower, as is my CRP. So far I've experienced no side effects that I'm aware of. But the tests done didn't include the particulates, so I have no way of knowing the statin's effect on dense LDL. Overall LDL is much lower, though. In your opinion, should I discontinue the pravastatin?
Patients taking statins for the first time are usually advised to make other lifestyle changes; less junk food, more exercise, stop smoking, drink less. This could well mask some risks.
Eating more olive oil, which supplies squalene, would replace some hormone precursors depleted by statins, but not Coq10 or K2.
Breathlessness, getting puffed more easily on exercise, is an initial sign of CoQ10 deficiency that should be more widely recognized.
10mg is not a large dose for pravastatin.
I think the concern is not that statins are any more toxic than other drugs - they are less toxic than the drugs they replace, apart from niacin.
The concern is that the benefits are hard to detect, and there can be a subtle reduction in the quality of life for some.
I'm curious to know what your before-and-after lipids were.
@ Roger in Texas:
It is true that millions of people, about 22% of the adult population I understand, are taking statin drugs. It is also true that millions of people quit taking statins every year because of the adverse side effects but do not report the adverse side effects to their doctors so the records on side effects are not complete. It is also true that millions of people complain to their doctors of adverse side effects each year but are convinced by their doctors that the side effects "could not be due to statin drugs" but are simply the natural effects of old age. (The doctors simply don't know any better.) I know many people who have started statin drugs and quit because of the side effects.
Ten years ago a cardiologist who has done extensive research on the side effects of statins, Dr. Peter Langsjoen, sent a petition to the FDA asking that a black box warning be included as part of statin package insert information. The following is part of what Dr. Langsjoen had to say about statins:
"Statins do three things:
1. They block the body's ability to make cholesterol, thus lowering the blood level of cholesterol, thereby curing cholesterol neurosis. Doctors and patients equally neurotic have immediate gratification. The "evil" high cholesterol has been dramatically lowered and the future is bright and promising. So far...so good.
2. Unrelated to their cholesterol lowering, statins have been found to have anti-inflammatory, plaque-stabilizing properties which have a slight benefit in coronary heart disease.
3. Statins kill people - lots of people - and they wound many, many more. All patients taking statins become depleted in Coenzyme Q10 (CoQ10), eventually - those patients who start with a relatively low CoQ10 levels (the elderly and patients with heart failure) begin to manifest signs/symptoms of CoQ10 deficiency relatively rapidly - in 6 to 12 months. Younger, healthier people who's only "illness" is the non-illness "hypercholesterolemia" can tolerate statins for several years before getting into trouble with fatigue, muscle weakness and soreness (usually with normal muscle enzyme CPK tests) and most ominously - heart failure."
There are many other adverse side effects of statin drugs besides impairment of coenenzyme Q10 synthesis.
Lipitor insert reveals increased risk of non-cardiac death, overall no advantage.
Michael Eades on statins
@George Henderson: Sorry I have been so long in getting back to this. You asked about my lipids before and after, and I just had testing done. Here are my results:
2/2010: TC: 215 LDL: 132 HDL: 69 Triglycerides: 70
2/2012: TC: 263 LDL: 167 HDL: 81 Tri: 122
8/2012: TC: 173 LDL: 95 HDL: 71 Tri: 73 (began statin mid-May)
1/2013; TC: 189 LDL: 100 HDL: 66 Tri: 97
To me, these numbers are almost meaningless. My cardiologist uses a service at Boston Heart, and I receive a 50-page analysis of each component and graphs showing the breakout of both HDL and LDL components. Those are useful. My CRP readings for the three periods were .24, .26 and .26 respectively.I expected the CRP reading to be lower after several months of pravastatin, but the 10mg dose is minimal.
So far, no side effects noted from the statin.
I've been following Dr. Eades' very low carb, high protein dietary guidelines for several years.
Pravastatin is a natural statin; there is increased risk of DVT, but I imagine this would be unlikely on a low-carb diet. It is clearly having the lipid-lowering effect. It is water soluble so should not affect cognition as lipitor does, but your diet should supply K2 anyway.
I can't help but wonder, if you are eating much the same as before, but your liver is making less lipids, where is the energy going?
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