Today I will be writing about an overview of some of the current medication available for lowering LDL cholesterol, as well as some medication that is no longer used.
I have already explained all the different types of cholesterol, or lipoproteins [here](https://tinyurl.com/bdz67ekp), and what fat actually is [here](https://tinyurl.com/32ahwcps). I will just say here that lowering cholesterol actually means lowering LDL cholesterol. There is currently no available medication that can increase your HDL (which should be a good thing).
**1. Statins**. Statins are some of the most prescribed drugs in modern medicine. Every healthy patient that is evaulated as having a "high" risk of heart disease should be prescribed a statin according to most guidelines - we call this primary prevention. Every heart attack survivor should be prescribed a maximum tolerated statin dose according to most guidelines - we call this secondary prevention. As of 2023, Lipitor is the 2nd most profitable drug in history. There is still enormous money to be made pushing statin prescriptions, despite the expired patent.
Since we have known for at least 50 years that dietary cholesterol does not significantly alter cholesterol levels in the blood, we needed to find a drug that would stop the body from creating its own cholesterol. Statins work by inhibiting the rate-limiting enzyme in cholesterol synthesis called HMG-CoA reductase.
Statins do indeed work as advertised - they do a brilliant job of lowering LDL cholesterol. Unfortunately, like all other drugs, statins have their side effects. It is known that they cause muscle aches, are potentially toxic for the liver, and now we know they are linked to dementia and possibly other neurological diseases, and why wouldn't they be? Remember that cholesterol is a vitally important molecule - over 40% of the cell membrane is composed of cholesterol, the myelin sheath surrounding our nerves is made of cholesterol; vitamin D, and ALL steroid hormones are made from cholesterol.
But, as a patinent, the most important thing you can ask your doctor is: "But, doc, how much longer will I live if I take this drug?", which should, of course, be followed by: "What are the side-effects?".
The answer to the first question are in - you gain ~3 days of life per 5 years of treatment for primary prevention, and ~4 days of life per 5 years of treatment for secondary prevention of heart disease. You can look at the study [here ](https://bmjopen.bmj.com/content/5/9/e007118.long). So, if you take Lipitor for 30 years straight, you will, on average, live ~18-24 days longer. If statins were free candy with no side-effects, I would have no objections, but, alas, this is not the case.
Should you take a statin? Nobody can answer that for you. However, you have the right and the obligation to be well informed. Ask your doctor what he thinks, and if he is dismissive, then find another doctor. Personally, I will never take a statin, even if I survive a heart attack/stroke.
Statins are the best drugs of all lipid-lowering agents because they at least show *some* benefit in reducing heart disease risk. This probably says a lot about the other drug classes we will be discussing next.
**2. Ezetimibe.** Remember how dietary cholesterol does not significantly alter blood cholesterol levels? Well imagine if you could reduce this small effect even further! Ezetimibe works by decreasing cholesterol absorbtion in the intestines. Does ezetimibe help lower LDL? Yes, yes it does. Does it affect overall mortality? [No, it does not](https://drnevillewilson.com/2008/02/04/the-enhance-trial-its-failure-concerns/). Ask your doctor how much longer will you live if you take ezetimibe - the answer is actually zero days.
**3.PCSK9 inhibitors.** So, you are taking a statin and ezetimibe, and your cholesterol is still too high according to the ever lowering upper limit of acceptable cholesterol levels? No problem, we will give you an extremely expensive monoclonal antibody that will affect your LDL receptors. These drugs are a special class of useless. Not only do they cost a lot of money, they have a negative to no effect whatsoever on overall mortality. How much longer will you live if you take Repatha? Probably 0 days or less, but ask your doctor and they probably won't know.
To truly understand this, it might be a good idea to read "A Statin Nation" by coleague M. Kendrick. The efficacy of Repatha (A PCSK9 inhibitor class drug) was 'proved' in the FOURIER trial, which used something called 'composite end-points', meaning that the researchers packaged different, related clinical outcomes... with coronary revascularization, which isn't a clinical outcome. Yes, the FOURIER trial showed an improvement in the COMPOSITE end point of: cardiovascular death, cardiac infarction, stroke, unstable angina hospitalisation AND coronary revascularization; but the total number of OVERALL deaths and the total number of CARDIOVASCULAR-related deaths was higher in the Repatha group compared to placebo.
And this is it, we have currently three main drug classes that will reduce your LDL cholesterol levels, but I think we should mention another, forgotten, drug class as well.
**4. Trapibs.** Trapibs were a class of drugs that were in development in the mid to late 2000s, but were since scraped, abandoned and forgotten. We were not taught about them in med school. Abandoned drugs are just an unimportant footnote in medical school, anyway; which is a shame because a lot can be learned through studying failure.
Anyway, trapibs affect the interaction of HDL and LDL particles through an enzyme called CETP. They ultimately increase HDL, which is good, and also lower LDL, which is also good. Here we have drugs that should work amazingly well on paper - they decrease LDL similar to statins, and they also increase HDL. Yet, their effect on overall and cardiovacular mortality is close to zero.
None of the above described LDL-lowering agents have a significant, if any, effect on overall mortality, yet we still continue prescribing them to patients. Sure, there were studies that found an association between high LDL levels and cardiovascular mortality; but there's a far stronger association with either diabetes, smoking, obesity and hypertension. You should always verify information for yourself, especially when it comes to health, but it is my opinion that lipoproteins are, at best, a mere marker of potential heart disease risk, and a complete red herring at worst. It's like the correlation between yellow fingers and lung cancer. Should we cut off yellow fingers? No, of course not. It just so happens that smokers usually get yellow fingers from excessive smoking. Should we reduce LDL cholesterol by substituting animal fats with industrial made seed oils? I leave that for you to decide.
As always, if you liked the content, don't forget to boost and follow, maybe throw some sats my way.
Agree. These medications probably have little value. See a cohort study: Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality. The Global Cardiovascular Risk Consortium*published in NEJM 10/2023 about cardiovascular risk factors. Notice the graphics in particular that compare risks of cardiac events and death with relation to BMI, BP, smoking, diabetes, and non-HDL cholesterol. Some signal for stroke and heart attack, but no difference in hazard ratios for death with non-HDL cholesterol risk factor. One might wonder that a stroke could be worse than death if you are debilitated after the stroke, of course. Diabetes is the strongest risk factor in this study, BY FAR. I have heard of the increased risk of diabetes with statin medications and am not sure if this is causation or association. I would sure hate to prescribe a statin if it increases risk for diabetes, as this sounds like a risky move. As a family physician, I lay out this controversy to actively involve the patient in the decision, but I do not strongly recommend lipid lowering medications due to the side effect profile and non-effectiveness in general.
Vlada,
Very detailed explanation of the metabolism of cholesterol and triglycerides. Good Job! When I am trying to explain this to my patients, of course, I have to skip multiple steps of this discussion. I do focus on the insulin piece and inform them that high insulin levels prevent weight loss and causes weight gain. I also stress, as you mentioned, dietary intake of cholesterol and triglycerides, has little effect on these numbers, instead, focus on carbohydrate intake to move the needle. I include in my discussion, that total LDL mass may not be a great measure and talk about large buoyant LDL vs. small dense LDL (seems to be evidence of a difference in risk). I let them know that low-carb, high-fat diet causes a shift from small-dense to large buoyant LDL in most. I discuss how the circulating apo B proteins become altered in a high glucose environment, preventing the liver reuptake receptors from recognizing them, resulting in a longer time in circulation, more opportunity for oxidation, and hence theoretically, more likelihood of atherosclerosis. I also acknowledge that almost all other physicians will try to prescribe a statin or other medication to lower their LDL. I tell them that these will indeed lower the LDL cholesterol. I am very skeptical that these reduce mortality risk, however. We discuss statin side effects, as well. In those patients that fit the phenotype of lean-mass hyper-responders (see Dave Feldman's work) and are also low-carb, high-fat eaters(which I am one), I counsel them about risk. Sometimes, we even get a CAC score for further clarification and tracking. I admit, I took the wrong approach for 20+years in medicine, but I feel that you and I are on the correct path now. This is an uphill battle against the established dogma, stay strong and true!
hello test user
Very accurate! Research is tainted. I don't debate that statins lower LDL, I think they do. This reduction does not equate to reduced morbidity or mortality though. Even through that lens, if you look at absolute risk reduction (instead of relative risk reduction) in these statin trials, it is dismal-as a population, mind you, possibly gain 30 days of life in the most generous interpretation of the data. My wife saw a diagnosis on a patient chart the other day that had a diagnosis of "intolerance to statin". She is a physical therapist who has joined me in the quest for truth. She joked, "it is like you are SUPPOSED to take these medications, your body does not have enough statins." I think this speaks to how far this medical misinformation has gone. I am not afraid to tell my patients that I feel that triglycerides and VLDL cholesterol are more important and a great marker for insulin triggering and glucose load. I explain the VLDL, triglyceride, sugar connection. I also warn them that other doctors will likely immediately recommend you take a statin if they see you. I tell the patients why, so they are prepared, because it is confusing. For me, bitcoin lead me to Twitter. Twitter lead me to stumble across the low-carb, high-fat community and the rest is history.
Thanks! I am impressed with your content also! We have a similar mind-set in practice.
Vlada,
See my post about carbohydrate addiction.
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Vlada,
See my post about carbohydrate addiction.
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Vlada,
Here is a link to my newest post regarding creatine.
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Lowcarbdoctor
I agree, testosterone is vital! I am a physician who treats men and women with bioidentical hormones. Investigate BioTe if you are interested. I am a BioTe provider. I replace hormones with pellet insertions under the skin. This treatment can literally recover lost years of quality of life for my patients!
Great overview of exercise!
Very helpful list of items that can allow for success in life!
Solid recommendations!
Great advice!
Insan,
Thank you for this information! I am a physician also interested in immune function. I have enclosed NOSTR links to some of my posts regarding immune function. Enjoy!
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naddr1qqxnzd3exs6rwwp3xs6rvwpjqgs9krs286qp5gndrpcqj40njmeq26hlydnuqyyxw0fnztl8fa56myqrqsqqqa28pcv7x7
Vlada,
Nice nutritional review! If you are interested, watch my Williams Family Medicine YouTube channel video on fructose.
This diet works for most people!
Vlada,
Nice article! I have printed metabolic syndrome pages in my exam rooms. I circle how many of the 5 criteria that they have when I am with a patient in the room. This starts the process of helping the patients think through where they are headed if they don't make a change. I use this opportunity to give them a vision for a different life and healthy choices.
Agree! I rank DM as the highest risk for ASCVD! If we can lower triglycerides and VLDL cholesterol with low-carb diet, then we theoretically decrease the possibility of the VLDL becoming small dense LDL, decrease risk of damage (oxidation) of the LDL particle and likely invading the blood vessel wall in an inflammatory way preventing badness. After I switched to low-carb, high-fat, my total and LDL cholesterol jumped up massively, but my triglycerides and VLDL are quite low. I had a coronary calcium score for my own information and it is zero and I am 53 years old. Suffice it to say, I will not be taking a statin medication. You will find this humorous, my 2nd labwork was performed at a different lab than my first. At the bottom of my lab printout it stated, consider workup for familial hypercholesterolemia.
Vlada,
Some other books to consider if you have not read them in no particular order: Jason Fung: The Diabetes Code, The Obesity Code, The Complete Guide to Fasting; Gary Taubes: Good Calories, Bad Calories (one of my favorites-similar to Teicholz); Ivor Cummins: Eat Rich, Live Long; Tim Noakes: The Real Meal Revolution; Eric Westman: End Your Carb Confusion. The more I read, the more I am convinced that this is the correct prescription for our patients.