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Friday, January 19, 2018

Statins: Sugar-Coating the Truth

A priest, a rabbi, too a cardiologist walk into a bar.

No, that’s non it…

Why did the cholesterol cross the road?

Nope, that’s non it either…

Did you lot listen the ane nigh statins too increased withdraw a opportunity for type 2 diabetes?

YES! That’s the ane I meant. Only, this isn’t a joke.

Statin drug exercise is forthwith associated amongst an increased withdraw a opportunity for developing type 2 diabetes. Is this just fearmongering headlines, or is at that spot genuinely something to it?

At some point, I volition write some other postal service (or ii or three) nigh the myriad horrible effects of statin drugs. Today, I’d similar to focus on ane specific unintended effect of our insanely misguided too biochemically ridiculous “war on cholesterol.” (It seems similar most of my readership is already pretty familiar amongst how of import cholesterol is to just nigh every unmarried thing the torso does. If you’re novel here, I’m distressing that this tidings powerfulness daze and/or confuse you. Like I said, I’ll embrace the nuts & bolts of it some other time. For now, suffice it to tell that if you’ve found my weblog because you’ve come upwards to realize that everything nosotros thought we knew about saturated fat, depression calorie diets, too things similar that, is completely backward, just know that the same is truthful for cholesterol. Bottom line: cholesterol is the unmarried most misunderstood, maligned, too wrongfully defendant nutrient inwards all of wellness science.)

Okay. Recently, a study came out that indicated a important increment inwards the withdraw a opportunity of developing type 2 diabetes amid manful mortal statin users, ages 45-73. (Not just statistically significant, but clinically significant, important it genuinely matters inwards the existent world, too non just to eggheads inwards labs looking for grant coin to fund their adjacent study.[Just kiddin', researchers. You know I honey ya! My weblog wouldn't be without you.]) The foremost thing to know is that this shouldn’t surprise anyone. It’s form of quondam news, actually. It’s been known for a few years forthwith that this is a possibility. It’s non a huge possibility, but the association betwixt statin drug handling too developing T2D is strong plenty that fifty-fifty the U.S. Food too Drug Administration (FDA) acknowledges that statins may final result inwards elevated blood glucose too hemoglobin A1c. The highly respected Mayo Clinic (one of the premier medical institutions inwards the U.S., for those of you lot who’ve never heard of it) also lists “increased blood sugar or type 2 diabetes amid the potential side-effects of statins. (Also: liver damage, musculus damage, digestive problems, too neurological side-effects, but motility along! Nothing to meet here! FFS…)

Now, before nosotros acquire into why drugs that lower cholesterol powerfulness have got an effect on blood sugar, let’s dissect the study a fiddling further.

According to the authors, compared to subjects non taking statins, those receiving statin therapy had a 46% increased withdraw a opportunity for type 2 diabetes during the 6-year follow-up, amongst the withdraw a opportunity specified equally dose-dependent for those taking simvastatin too atorvastatin. (Meaning, the higher the dose, the greater the withdraw a opportunity for developing the dreaded diabeetus.) Among the men receiving statin treatment, insulin sensitivity was decreased past times 24% too insulin secretion decreased past times 12% compared to individuals non beingness treated amongst statins, amongst these effects also beingness dose-dependent for simvastatin too atorvastatin.

Out of a total of 8,749 subjects, 625 received novel diagnoses of type 2 diabetes. Here's how it broke down:

Total subjects: 8,749
Total novel T2D diagnoses subsequently 6-yr follow up: 625

Subjects non taking statins: 6,607
Non-statin takers who developed diabetes: 386 (5.84%)

Total taking statins: 2,142
Statin-takers who developed diabetes: 239 (11.16%)

However, at baseline (that is, the start of the study) compared to subjects who did not receive diabetes diagnoses during the follow-up years, the grouping of people who became diabetic were older, to a greater extent than overweight, less physically active, had lower HDL levels, higher fasting blood glucose too HbA1c, higher triglycerides, worse answer to an oral glucose tolerance test, too had a greater per centum of smokers. So these subjects were at greater withdraw a opportunity for developing type 2 diabetes (or metabolic syndrome, or pump disease, or just manifestly dropping dead) regardless of whether they were taking a statin or not. This doesn’t negate a potential role for statins inwards contributing even further to the withdraw a opportunity for diabetes, but I desire to last intellectually honest hither too dot out that these subjects were already at a higher risk.

BUT: according to the researchers, fifty-fifty when they controlled for these factors—however it was they managed to attain that—the subjects treated amongst statins still had a greater withdraw a opportunity for developing diabetes. (Don’t enquire me nigh controlling, too p-values, confidence intervals, too blah, blah, blah. I know only enough statistics to brand me dangerous.)

Yes, Virginia, There Is a Connection

Now that I’ve done my due diligence, let’s meet why there’s a correlation betwixt statin exercise too withdraw a opportunity for diabetes. Again, we’re trying to decide if there’s a plausible biochemical or physiological machinery that powerfulness explicate this. I spend upwards to participate inwards nonsense like, “Meat rots inwards the colon,” which has no scientific footing whatsoever. If I’m maxim something damning nigh a pharmaceutical drug that tens of millions of people have got every 24-hour interval (and which I track against inwards my book), thence I had darn good improve dorsum it upwards amongst some actual facts, right?  So hither goes.

The link betwixt statins too diabetes tin last summed upwards inwards ii words: prenylated proteins. If you lot have got no stance what these things are, too you’ve never heard the term “prenylation,” you’re non alone. I tin almost guarantee most doctors who prescribe statins on a daily footing have got never heard this term, either. And that is a disaster, Here’s why:

“Statin” is a generic term for drugs that inhibit the enzyme HMG CoA reductase. HMG CoA reductase plant its biochemical project real early inwards a long, complex pathway called in this nifty diagram past times Chris Masterjohn, PhD. All I tin tell is, when it comes to cholesterol, this dude knows his stuff.)

And here’s a diagram, amongst pertinent items circled for our learning convenience:

Image past times Sav vas (Own work) [CC0], via Wikimedia Commons

First, hold back for “STATINS,” inwards the regal box toward the laissez passer on left. Notice how high upwards inwards the pathway they exert their effects. Second, hold back for cholesterol, waaaay downwardly at the bottom, circled inwards green. The cardinal thing to empathize nigh this is, statins don’t only block the production of cholesterol. They block production of everything else that’s supposed to acquire produced along the way, too.

Before nosotros laissez passer on off to the diabetes connection, let’s hold back way downwardly at the bottom again. You’ll meet “ubiquinones” circled inwards yellow. I’m generalizing here, but think of “ubiquinones” equally coenzyme Q10, which is an essential molecule involved inwards the mitochondrial electron carry chain. (As detailed in this postal service from the cancer series. Yeah…if you’re thinking that statins could maybe, just maybe also increment cancer risk, since they disrupt the synthesis of something required for healthy mitochondrial function, I can’t confirm for certainly that you’re right, but let’s just tell I’m giving you lot a virtual high-five. I swear, you lot can’t brand this materials up…)

The Statin-Diabetes Link

Now, let’s acquire dorsum to diabetes too that weird “prenylated proteins” thing. Down toward the bottom of the mevalonate pathway diagram (again, the end of a pathway that statins disrupt much earlier), you lot volition meet 3 things circeled inwards red: farnesyl-PP, geranylgeranyl-PP, too prenylated proteins. You don’t demand to empathize precisely what these things are. For our purposes of learning the physiological machinery past times which statins powerfulness increment withdraw a opportunity for diabetes, it’s plenty to know that these compounds are required for glucose-stimulated secretion of insulin past times the pancreatic beta-cells. Yes, the cells that secrete insulin demand these prenylated proteins inwards lodge to business office properly. Finally, we’re getting somewhere!

I managed to dig upwards some studies that flora a connexion betwixt farnesyl-PP, geranylgeranyl-PP, too “G proteins” that assist beta-cells attain their job. (From what I tin empathize of the studies, these “G proteins” are involved inwards getting the beta-cells to secrete insulin inwards answer to rising blood glucose. Just similar an insulin receptor, they have got to last translocated (moved) from where they’re produced within the cell, over to the jail cellular telephone membrane. And what triggers them to attain this is the prenylation step, which requires farnesyl-PP too geranylgeranyl-PP. No prenylation --> no translocation of G proteins --> no secretion of insulin. (And inwards example anyone doesn’t meet the final connexion here: no secretion of insulin way blood glucose stays elevated for longer than it should, leading to chronic hyperglycemia, elevated hemoglobin A1c, too quite maybe an eventual diagnosis of type 2 diabetes. Nice, huh?)

Additional Important “Stuff”
(¡Muy Importante!)

Two to a greater extent than things:

This is Human Body 101.
Why does the average statin-shilling 

cardiologist have NO CLUE?
  1. What statin drugs attain is block the endogenous synthesis of cholesterol. (That is, the cholesterol our bodies create within us.) They have got no effect on the cholesterol nosotros acquire from foods. So spell somoene on a statin who eats a lot of cholesterol-rich foods powerfulness last able to overcome the laundry listing of heinous side effects of statins that come upwards nigh due to depletion of cholesterol, they tin not ameliorate the effects that are due to depletion of some other chemical compound way at the bottom of that pathway. (This is why everyone on a statin should last taking a CoQ10 supplement.)
  2. Statins don’t completely, 100% block the mevalonate pathway. They are called HMG CoA reductase inhibitors, non HMG CoA reductase stoppers, or nullifiers. So the pathway soundless goes forward, but not equally much equally it is supposed to. So some cholesterol, too some CoQ10, too some prenylated proteins soundless acquire manufactured—just not equally much equally the torso probable needs. (Think nigh it: if cholesterol production were completely near downwardly past times statins, too someone taking a statin was next an extremely low-cholesterol diet…you know the type…vegan; egg-whites only; margarine; skinless white meat chicken, etc.—they would in all likelihood drib dead inwards brusque order, since nosotros demand cholesterol for every unmarried jail cellular telephone too mitochondrial membrane inwards our body. And nervus function. And encephalon function. And synthesis of testosterone, estrogen, progesterone, cortisol, aldosterone, vitamin D, too more. But I digress. I’ll salve that rant for when I write inwards to a greater extent than special nigh cholesterol someday.)

Regardless of whether statins block this pathway or just “inhibit” it, forthwith you lot tin meet that at that spot is, inwards fact, a physiological machinery past times which these drugs powerfulness real good increment someone’s withdraw a opportunity for diabetes.

P.S. If you lot are interested inwards totally geeking out on this stuff, you lot should check out this paper. Here’s the abstract, which is incredible inwards its forthright condemnation of statins inwards causing rhabdomyolysis. (That’s a fancy discussion for “muscle destruction,” which, you’ll holler back from way dorsum at the showtime of this post, the FDA too Mayo Clinic both recognize equally a side effect of statin use.)

(Emphasis below is mine.)
Abstract: Rhabdomyolysis is a rare, but serious complication of statin therapy, too represents the most severe halt of the spectrum of statin-induced myotoxicity. We study a example where coenzyme Q10 facilitated recovery from statin-induced rhabdomyolysis too acuate renal failure, which had initially persisted despite statin cessation too haemodialysis. This observation is biologically plausible due to the recognised importance of coenzyme Q10 inwards mitochondrial bioenergetics within myocytes, too the fact that statins inhibit farnesyl pyrophosphate production, a biochemical pace crucial for coenzyme Q10 synthesis. 

(In example you lot didn't quite pick out grip of the biggie upwards there, way beyond fifty-fifty the musculus impairment -- STATIN INDUCED ACUTE RENAL FAILURE?! HELLO!! Know what that means? Youll have got the lowest cholesterol inwards the dialysis ward! Congratulations!!)

P.P.S. If you lot desire to geek out even further, all you lot genuinely demand to attain is read the awesome championship of some other paper: The change of poly peptide prenylation induces cardiomyocyte hypertrophy through Rheb-mTORC1 signalling too leads to chronic pump failure. (Yes, the change of poly peptide prenylation tin Pb to pump failure. I said it before, too I can’t assist maxim it again: You can’t brand this materials up! Modern medicine is SO FREAKING BACKWARD. There is NO share of human wellness that statin drugs attain non compromise.)

Remember: Amy Berger, M.S., NTP, is non a physician too , LLC, is non a medical practice. The data contained on this site is non intended to diagnose, treat, cure, or preclude whatever medical condition.


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