Statins: A Wonder Drug?

Know the metabolic and neurological risks

In 2020 statins became a $1 trillion industry…let that sink in.(1)

This relatively unknown medical statistic makes them highly profitable to the point where proponents of statins, much like zealots of other forms of pharmaceutical interventions, would like them put in the water supply.(2) I wish I was joking.

All of that of course presupposes that cholesterol is the bane of human existence and if we could just keep lowering it to pathological levels, all would be right in the world. I have seen countless articles written on their miraculous benefits from writers who have clearly never read a paper or taken a biochemistry course in their careers. The truth is that I could write a book on this topic but lucky for you there are some great ones already out there from people like Dr Malcolm Kendrick and others, so I will spare you the thesis length article here. I will however highlight a few papers I think are worth noting for a more nuanced understanding of the side effects of statin use as this is generally downplayed by public health officials and doctors…déjà vu anyone?

The first is a wonderful interventional pilot study from 2012 in the American Journal of Geriatric Pharmacotherapy. In this 12 week study the aim of researchers was to evaluate the impact on cognition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor (statin) discontinuation and rechallenge in individuals with Alzheimer's dementia (AD) on statins at baseline.(3) This is important. Especially the rechallenge because it can truly help eliminate confounding variables if you reintroduce a therapy and find the same side effect that disappeared during the discontinuation phase.

In the study, eighteen older adults underwent a 6-week withdrawal phase of statins followed by a 6-week rechallenge. The primary outcome measure was cognition, measured by the Mini-Mental State Examination (MMSE). Secondary outcome measures were the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery, Activities of Daily Living (ADL) scale, Instrumental ADL (IADL) scale, and fasting cholesterol. 

What was found may surprise you. The study found an improvement in cognition with discontinuation of statins and worsening with rechallenge. This is of course coupled with an inverse relationship between total cholesterol and the statin use. I said this may surprise you if you didn’t know that high cholesterol in late life was associated with decreased dementia risk.(4)

In fact, examination of cholesterol levels in a 2005 paper in Neurology showed that the risk reduction was apparent only among the highest quartile at ages:

·        70 (8.03 to 11.44 mmol/L [311 to 442 mg/dL]

·        75 (7.03 to 9.29 mmol/L [272 to 359 mg/dL]

·        79 (6.82 to 9.10 mmol/L [264 to 352 mg/dL]

Some of you may think those cholesterol levels are off the charts but that would also be because we have all been convinced of the simple and unproven fact that lower = better when it comes to cholesterol. The last point I will make here is that that fine tuning of neural cholesterol dynamics is essential for basic synapse function, plasticity and behavior. This is clearly interrupted with statin therapy that can cross the blood brain barrier and breaks in cholesterol homeostasis is the unifying primary cause of a variety of neurodegenerative diseases including Alzheimer's disease.(5)

So now let’s move to a brand new paper (July 2023) in Cureus which was a systematic review aiming to comprehensively explore the link between the use of statins and insulin intolerance. From the paper…“The included studies had a total of 46,728,889 participants. The findings suggest that the use of statins is associated with a decrease in insulin sensitivity and insulin resistance. This systematic review provides evidence that the use of statins may have an adverse effect on insulin sensitivity and increase insulin resistance.”(6)

This is a stroke of irony because hyperinsulinemia(chronically elevated insulin levels) is a risk factor itself for cardiovascular disease.(7) To make matters worse statin use affects fasting glucose concentrations, and fasting insulin is dose-dependent manner. So the higher dose the worse the biomarkers. I didn’t even mention that the METSIM study found that statin therapy was associated with a 46% increased risk of T2DM along with worsening of hyperglycemia in men and up to a 48% increase in women.(8,9)

How do we square this? Well we don’t really. The paradigm is wrong and yet again humans have oversimplified the body in order to create a simple, easily marketable and profitable solution. Pretty common really.

In the end the “cure” cannot be worse than the disease and in this case it is likely that even the supposed disease(hypercholesterolemia) is misunderstood. The punitive benefits from statin therapy are likely due to their anticoagulation and anti-inflammatory effects. All of which can be achieved through nutrition and lifestyle modifications.  In other words it is the pleotropic effect and not the result of their ability to lower cholesterol levels.

So what we have is yet another example of profits over people. Sadly I have seen this first hand at the hospital I worked at where statins were given out like candy, almost as if they had absolutely no down side. But when you have doctors calling these miracle drugs, you see just how far from science we have drifted.

The more you know.

References

1.      https://www.bmj.com/company/newsroom/for-most-healthy-people-benefits-of-statins-may-be-marginal-at-best/. Accessed July 22, 2023.

2.      Ginter E, Kajaba I, Sauša M. Statíny do pitnej vody? Riziko vedľajších účinkov a nízkych hladín cholesterolu [Addition of statins into the public water supply? Risks of side effects and low cholesterol levels]. Cas Lek Cesk. 2012;151(5):243-247.

3.      Padala KP, Padala PR, McNeilly DP, Geske JA, Sullivan DH, Potter JF. The effect of HMG-CoA reductase inhibitors on cognition in patients with Alzheimer's dementia: a prospective withdrawal and rechallenge pilot study. Am J Geriatr Pharmacother. 2012;10(5):296-302. doi:10.1016/j.amjopharm.2012.08.002

4.      Mielke MM, Zandi PP, Sjögren M, et al. High total cholesterol levels in late life associated with a reduced risk of dementia. Neurology. 2005;64(10):1689-1695. doi:10.1212/01.WNL.0000161870.78572.A5

5.      Koudinov AR, Koudinova NV. Cholesterol homeostasis failure as a unifying cause of synaptic degeneration. J Neurol Sci. 2005;229-230:233-240. doi:10.1016/j.jns.2004.11.036

6.      Dabhi KN, Gohil NV, Tanveer N, et al. Assessing the Link Between Statins and Insulin Intolerance: A Systematic Review. Cureus. 2023;15(7):e42029. Published 2023 Jul 17. doi:10.7759/cureus.42029

7.      Adeva-Andany MM, Martínez-Rodríguez J, González-Lucán M, Fernández-Fernández C, Castro-Quintela E. Insulin resistance is a cardiovascular risk factor in humans. Diabetes Metab Syndr. 2019;13(2):1449-1455. doi:10.1016/j.dsx.2019.02.023

8.      Galicia-Garcia U, Jebari S, Larrea-Sebal A, et al. Statin Treatment-Induced Development of Type 2 Diabetes: From Clinical Evidence to Mechanistic Insights. Int J Mol Sci. 2020;21(13):4725. Published 2020 Jul 2. doi:10.3390/ijms21134725

9.      Statin use linked to increased risk of diabetes in older women. Risk of type 2 diabetes in postmenopausal women may be up to 48 percent higher than in women who do not use the cholesterol-lowering drugs, but the jury tilts in favor of continuing medication. Duke Med Health News. 2012;18(4):4-5.