Cholesterol denialism

{{pseudosciencenav}} 
{{hatnote|For the polar opposite fallacy, see [[dietary cholesterol]].}}

'''Cholesterol denialism''' is a form of [[Pseudoscience|pseudoscientific]] [[denialism]] that asserts that high blood LDL cholesterol levels do not increase the risk of cardiovascular disease.<ref>[https://archive.is/0rOqj Cholesterol Denialism is Pseudoscience]. medscape.com.</ref> A related idea known as '''statin denialism''' holds that statin usage does not reduce the likelihood of cardiovascular disease. Proponents claim that statins should be avoided because they are sold by [[Big Pharma]] and cause adverse side effects. It is promoted by [[carnivore diet]] and [[LCHF]] conspiracy theorists and has a presence on [[social media platforms]] such as [[Twitter]].

Cholesterol and statin deniers claim that saturated fat has wrongly been demonized by medical scientists and is healthy for dieting in very high quantities. They say that there is no link between LDL-C and total blood cholesterol levels and the risk of cardiovascular disease.<ref name="The Guardian">[https://www.theguardian.com/lifeandstyle/2018/oct/30/butter-nonsense-the-rise-of-the-cholesterol-deniers Butter nonsense: the rise of the cholesterol deniers]</ref> This view is contradicted by scientific evidence and has been described as bad science and dangerous.<ref name="The Guardian"/>

The leading advocates of cholesterol and statin denialism are associated with [[THINCS|The International Network of Cholesterol Skeptics]] (THINCS). They have been accused of "cherry-pick[ing] the scientific literature to find studies that support their theses, ignore the flaws in those studies, and ignore the vast body of literature that contradicts them."<ref name="denialism">[https://www.csicop.org/si/show/statin_denialism Statin Denialism]</ref> Statin denialists are known to exaggerate the side effects of statins and utilize scaremongering tactics.<ref>[https://sciencebasedmedicine.org/the-movie-cholesterol-the-great-bluff-is-an-exercise-in-denialism/ The Movie “Cholesterol: The Great Bluff” Is an Exercise in Denialism]</ref>

Low-density lipoprotein cholesterol (LDL-C) is an important causal risk factor for atherosclerotic cardiovascular disease.<ref>[https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.122.061010 Low-Density Lipoprotein Cholesterol Is Predominantly Associated With Atherosclerotic Cardiovascular Disease Events in Patients With Evidence of Coronary Atherosclerosis: The Western Denmark Heart Registry]. ahajournals.org.</ref> Global deaths attributable to high LDL-C increased from 3 million in 1990 to 4.4 million in 2019.<ref name="Global">[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218272/ Global Burden Attributable to High Low-Density Lipoprotein-Cholesterol From 1990 to 2019]</ref> {{wpl|Disability-adjusted life year|Disability-adjusted life years}} (DALYs) attributable to high LDL-C also increased from 69.7 million in 1990 to 98.6 million in 2019.<ref name="Global"/> In 2021, the World Heart Federation reported that elevated LDL-C contributed to 3.8 million CVD deaths.<ref>https://world-heart-federation.org/wp-content/uploads/World-Heart-Report-2023.pdf</ref> High LDL-C levels are also associated with increased dementia risk.<ref name="alzheimers">[https://www.alzheimers.org.uk/about-dementia/managing-the-risk-of-dementia/possible-risks-of-dementia/cholesterol Cholesterol and the risk of dementia]. alzheimers.org.uk.</ref><ref name="dementia">[https://jnnp.bmj.com/content/early/2025/03/21/jnnp-2024-334708 Low-density lipoprotein cholesterol levels and risk of incident dementia: a distributed network analysis using common data models]. jnnp.bmj.com.</ref>

==Criticism from the medical community==

Cholesterol and statin denialism is not taken seriously by the medical community. Poor adherence to statin therapy is linked to significantly increased risk of cardiovascular events and [[death]].<ref>Lansberg ''et al'' 2018. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5973378/ ''Nonadherence to statins: individualized intervention strategies outside the pill box'']. Vasc Health Risk Manag 14: 91–102.</ref>

In 2017, cholesterol denialist [[Aseem Malhotra]] and colleagues published an article which disputed the link between blood cholesterol levels and occurrence of heart disease. The authors also suggested that "stopping statins may paradoxically save more lives".<ref>Demasi, M; Lustig R. H; Malhotra A. (2017). [http://www.pharmaceutical-journal.com/opinion/insight/the-cholesterol-and-calorie-hypotheses-are-both-dead-it-is-time-to-focus-on-the-real-culprit-insulin-resistance/20203046.article "The cholesterol and calorie hypotheses are both dead — it is time to focus on the real culprit: insulin resistance"]. ''The Pharmaceutical Journal'' doi:10.1211/CP.2017.20203046.</ref> The article was criticized by the medical community. Cardiologist Tim Chico commented that "high cholesterol has been proven beyond all doubt to contribute to coronary artery disease and heart attack […] to say the cholesterol hypothesis is dead is simply incorrect."<ref>[http://www.sciencemediacentre.org/expert-reaction-to-new-report-on-statins-and-the-cholesterol-hypothesis/ Expert reaction to new report on statins and the cholesterol hypothesis]</ref>

Cardiologist Steven E. Nissen, has described statin denialism as an "internet-driven cult with deadly consequences."<ref>Nissen SE. (2017). [https://theskepticalcardiologist.files.wordpress.com/2017/08/aimed.pdf "Statin Denial: An Internet-Driven Cult With Deadly Consequences"]. Ann Intern Med. 2017 Aug 15;167(4): 281-282.</ref> He has also written that "we have abundant scientific evidence demonstrating that treatment of high risk primary prevention patients substantially reduces the risk of cardiovascular morbidity." Whilst acknowledging that statins, like other drugs, have adverse effects, "the benefits are so well documented that every effort should be made to encourage use of these drugs in appropriate patients."<ref>[https://www.medpagetoday.com/cardiology/cardiobrief/66863 Nissen Calls Statin Denialism A Deadly Internet-Driven Cult]</ref>

Professor of Medicine and Epidemiology Rory Collins has compared statin denialism to [[flat earth]]ism, he has noted "the claims that blood LDL cholesterol levels are not causally related to cardiovascular disease (which is really in the same realm as claiming that [[smoking]] does not cause [[cancer]]) are factually false."<ref name="The Guardian"/>

James Stein, a Professor of Cardiovascular Research has stated that "many lives have been lost or impaired because of statin non-compliance."<ref>[https://www.medicine.wisc.edu/vital-signs/dr-james-stein-speaks-out-against-statin-denialism Dr. James Stein Speaks Out Against "Statin Denialism"]</ref> In 2019, a joint editorial was published in the top cardiovascular journals around the world to warn people about the medical misinformation of statin denialism found on social media.<ref>[https://vascularnews.com/editors-in-chief-of-major-cardiovascular-journals-claim-medical-misinformation-puts-lives-at-stake/ Editors-in-chief of major cardiovascular journals claim medical misinformation puts “lives at stake”].</ref><ref>Hill JA, ''et al''. [https://academic.oup.com/ehjcvp/article/5/2/62/5301294 ''Medical misinformation: vet the message!'']. European Heart Journal - Cardiovascular Pharmacotherapy 5 (2): 62-63.</ref><ref>[https://www.ahajournals.org/circ/medical-misinformation Medical Misinformation: Vet the Message!]. List of the journals that have published the editorial.</ref>

== "But they're measuring the wrong things!" ==

Blood levels of LDL cholesterol (the "bad" cholesterol correlated with heart disease) are typically calculated by measuring total blood cholesterol (in mg/dL in the U.S. and mmol/L elsewhere), subtracting the measured amount of HDL cholesterol, and further subtracting a constant fraction of the measured blood triglycerides.<ref>[https://www.docsopinion.com/2019/02/23/ldl-cholesterol/ LDL-Cholesterol – The “Bad” Cholesterol Explained], Sigurdsson, ''Doc's Opinion'', 24-Mar-2019</ref>

While this is good enough for most people, cholesterol denialists aren't most people.  They'll claim that it's the ratio of LDL cholesterol to HDL cholesterol, not the absolute amounts, that matter, and therefore cholesterol doesn't cause heart disease.  They'll claim that the triglyceride-to-cholesterol ratio isn't always constant, which screws up the calculation for LDL cholesterol levels, therefore cholesterol doesn't cause heart disease.  They'll claim that it's the LDL particle count (LDL-P), not the LDL cholesterol level (LDL-C) that matters, therefore cholesterol doesn't cause heart disease.<ref>[https://chriskresser.com/the-diet-heart-myth-why-everyone-should-know-their-ldl-particle-number/ The Diet-Heart Myth: Why Everyone Should Know Their LDL Particle Number], Chris Kresser, 17-March-2019</ref>  They'll claim that there are two kinds of LDL cholesterol molecules -- large and fluffy, versus small and dense -- and that therefore cholesterol doesn't cause heart disease.  I think you can see the pattern here.

In recent years cholesterol denialists such as [[Eric Berg]] and Ben Bikman now accept that "small dense" LDL-particles cause heart disease but claim that high LDL-C is perfectly fine and there is only a concern if the LDL-particles are small. They both advocate LDL-P (particle number) testing. Eric Berg goes as far as calling large LDL particles "good".<ref>[https://www.drberg.com/blog/you-have-good-and-bad-ldl You Have Good and Bad LDL]. drberg.com.</ref> Whilst small dense LDL particles are considered "more" atherogenic than large buoyant LDL particles; all LDL particles are atherogenic.<ref name="Narrative Review">[https://pubmed.ncbi.nlm.nih.gov/31642874/ Apolipoprotein B Particles and Cardiovascular Disease: A Narrative Review]. pubmed.ncbi.nlm.nih.gov.</ref><ref>[https://www.ahajournals.org/doi/10.1161/01.cir.0000131511.50734.44 Atherogenic Lipoprotein Particles in Atherosclerosis]. ahajournals.org.</ref> All LDL particles are equally able to cause atherosclerosis but this is ignored by cholesterol denialists. For example the 2020 European Atherosclerosis Society Consensus Panel states that "All LDL particles exert atherogenicity to variable degrees, which can be influenced by the proteome, lipidome, proteoglycan binding, aggregability, and oxidative susceptibility".<ref name="2020 review">[https://academic.oup.com/eurheartj/article/41/24/2313/5735221 Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel]. academic.oup.com.</ref> Cholesterol denialists do not mention that medium size LDL particles increase CVD risk.<ref>[https://www.sciencedirect.com/science/article/abs/pii/S0167527317378841 LDL particle size and composition and incident cardiovascular disease in a South-European population: The Hortega-Liposcale Follow-up Study]. sciencedirect.com.</ref>

Large fluffy LDL particles, while less easily retained in the artery wall, deposit more cholesterol per particle so they are not "good". In reality it doesn't matter if LDL particles are small dense or large, what matters is the total number of LDL particles (total number of ApoB-containing lipoproteins, which includes all forms of LDL).<ref name="Narrative Review"/><ref name="2020 review"/><ref>[https://www.dralo.net/blog/ldl-particle-size Does LDL Particle Size Matter?]. dralo.net.</ref><ref>[https://www.youtube.com/watch?v=kplh30RmYo8 LDL size and Heart Disease (small dense vs large "fluffy") | Dr. William Cromwell]. youtube.com.</ref> To reduce cardiovascular risk, the LDL-C needs to be lowered overall.<ref name="2017 review"/><ref name="2020 review"/> Cholesterol denialists advice of promoting high LDL-C is potentially dangerous and likely to increase CVD events.

==Lipoproteins==

Lipoproteins are particles that transport cholesterol and other lipids through the bloodstream. Plasma lipoprotein particles are commonly divided into five main classes. They are, HDL, LDL, IDL, VLDL and chylomicrons. 

===LDL-C and ApoB===

There is a strong medical consensus from clinical trials and human Mendelian randomization studies that LDL-C is causally related to atherosclerotic cardiovascular disease, and that lowering LDL and ApoB-containing lipoproteins as much as possible reduces cardiovascular events.<ref>[https://pubmed.ncbi.nlm.nih.gov/23083789/ Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: a Mendelian randomization analysis]. pubmed.ncbi.nlm.nih.gov.</ref><ref name="2019 guidelines">[https://academic.oup.com/eurheartj/article/41/1/111/5556353 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS)]. academic.oup.com.</ref> Apolipoprotein B (ApoB) is the primary apolipoprotein of chylomicrons, VLDL, Lp(a), IDL, and LDL particles. Higher levels of ApoB and LDL shorten healthspan in humans.<ref>[https://www.nature.com/articles/s42003-024-05887-2 Mendelian randomization reveals apolipoprotein B shortens healthspan and possibly increases risk for Alzheimer’s disease]. nature.com.</ref>

By 2012, many clinical trials had been done.<ref>[https://www.lipid.org/lipid-spin/summer-2022/lipid-hypothesis The Lipid Hypothesis]</ref> The Cholesterol Treatment Trialists' Collaboration confirmed the LDL-C hypothesis after examining data from 26 trials involving 170 000 participants. According to their meta-analysis:

{{quotebox|Further reductions in LDL cholesterol safely produce definite further reductions in the incidence of heart attack, of revascularisation, and of ischaemic stroke, with each 1·0 mmol/L reduction reducing the annual rate of these major vascular events by just over a fifth. There was no evidence of any threshold within the cholesterol range studied, suggesting that reduction of LDL cholesterol by 2–3 mmol/L would reduce risk by about 40–50%.<ref>[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988224/ Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials]. ncbi.nlm.nih.gov.</ref>}}

The European Atherosclerosis Society have stated in 2017:

{{quotebox|Separate meta-analyses of over 200 prospective cohort studies, Mendelian randomization studies, and randomized trials including more than 2 million participants with over 20 million person-years of follow-up and over 150 000 cardiovascular events demonstrate a remarkably consistent dose-dependent log-linear association between the absolute magnitude of exposure of the vasculature to LDL-C and the risk of ASCVD; and this effect appears to increase with increasing duration of exposure to LDL-C.<ref name="2017 review">[https://academic.oup.com/eurheartj/article/38/32/2459/3745109 Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel]</ref>}}

The medical consensus to reduce heart disease risk is that optimal LDL-c should be less than 100mg/dl and those with heart disease or many risk factors, below 70 mg/dL.<ref>[https://my.clevelandclinic.org/health/articles/11920-cholesterol-numbers-what-do-they-mean Cholesterol Numbers and What They Mean]</ref><ref>[https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/lipid-panel Lipid Panel]</ref> 

Cholesterol denialists ignore the fact that normal LDL-c is actually 20-40 mg/dl and that 50 to 70 mg/dl is normal for native hunter-gatherers, healthy human neonates, free-living primates, and other wild mammals.<ref name="2022 review">[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9482082/ There is urgent need to treat atherosclerotic cardiovascular disease risk earlier, more intensively, and with greater precision: A review of current practice and recommendations for improved effectiveness]</ref><ref name="Optimal">[https://www.sciencedirect.com/science/article/pii/S0735109704007168 Optimal low-density lipoprotein is 50 to 70 mg/dl: Lower is better and physiologically normal]. sciencedirect.com.</ref> The LDL levels of healthy newborns are in the 30 to 70 mg/dl range.<ref name="Optimal"/> Reports of atherosclerosis in individuals with lifelong low LDL-C levels are extremely rare. No known adverse events have been linked to very low LDL-C levels.<ref>[https://www.escardio.org/Councils/Council-for-Cardiology-Practice-(CCP)/Cardiopractice/lipidology-update-targets-and-timing-of-well-established-therapies Lipidology update: targets and timing of well-established therapies]. escardio.org.</ref>

A 2022 review in the ''American Journal of Preventive Cardiology'' reported:

{{quotebox|Humans were never meant to harbor the low-density lipoprotein cholesterol (LDL-C) levels that are now commonplace. In one series of 147 full-term neonates, the average LDL-C was 20 ± 10 mg/dL. Despite the extraordinary rate of development and need for myelination, even neonates need very little LDL-C. The fact that animals, non-human primates, and humans who maintain low cholesterol levels from early in life have very little atherosclerosis all suggest that a ‘normal’ non-atherogenic LDL-C level is 20–40 mg/dl. That is of course difficult to achieve in a modern society and, as described herein, is not necessary for most people.

Based on the log-linear relationship of LDL-C to the hazard ratio for an acute ASCVD event, the LDL-C level where no excess risk occurs is approximately 38 mg/dL or 1 mmol/L [64] (Fig. 1). This value is consistent with the LDL-C levels observed among hunter-gatherer populations. In the Framingham Study, the average LDL-C of a man presenting with an Acute Coronary Syndrome (ACS) is approximately 150 mg/dL. In the Cooper Center Longitudinal Study, even when LDL-C at baseline was < 100 mg/dL, there was a continuous rise in risk for Coronary Heart Disease (CHD) mortality over a mean follow-up time of 26.5 yrs. Hence, it is crucial that exposure to atherogenic lipoproteins be dramatically reduced early and over the long-term.<ref name="2022 review"/>}}

The lower the LDL-C, the lower the risk and fewer complications of atherosclerosis.<ref name="2022 review"/><ref>[https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.123.064041 How Low Can You Go? New Evidence Supports No Lower Bound to Low-Density Lipoprotein Cholesterol Level in Secondary Prevention]</ref> Studies have found that people with LDL-C of 150 to 160 mg/dl have a significant increased risk in the prevalence of atherosclerosis.<ref>[https://www.jacc.org/doi/10.1016/j.jacc.2017.10.024 Normal LDL-Cholesterol Levels Are Associated With Subclinical Atherosclerosis in the Absence of Risk Factors]</ref>

In 2019, the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) stated that the "LDL-C hypothesis" is no longer a hypothesis, it is an established fact:

{{quotebox|Several recent placebo-controlled clinical studies have shown that the addition of either ezetimibe or anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs) to statin therapy provides a further reduction in atherosclerotic cardiovascular disease (ASCVD) risk, which is directly and positively correlated with the incrementally achieved absolute LDL-C reduction. Furthermore, these clinical trials have clearly indicated that the lower the achieved LDL-C values, the lower the risk of future cardiovascular (CV) events, with no lower limit for LDL-C values, or ‘J’-curve effect... Human Mendelian randomization studies have demonstrated the critical role of LDL-C, and other cholesterol-rich ApoB-containing lipoproteins, in atherosclerotic plaque formation and related subsequent CV events. Thus, there is no longer an ‘LDL-C hypothesis’, but established facts that increased LDL-C values are causally related to ASCVD, and that lowering LDL particles and other ApoB-containing lipoproteins as much as possible reduces CV events.<ref name="2019 guidelines"/>}}

The above is supported by current textbooks on lipidology. For example, ''Clinical Lipidology: A Companion to Braunwald's Heart Disease'' (third edition), published in 2024 states:

{{quotebox|The first and most relevant update presented in the 2019 guidelines concerns the old concept of an “LDL-C hypothesis,” which is now replaced by the established causal role of elevated LDL-C levels in ASCVD. Besides this causal role, genetic studies have introduced the concept of exposure time, revealing that LDL-C also has a cumulative effect on the risk of ASCVD9, a longer-term exposure leads to a greater retention over time of LDL particles (or, more generally, proatherogenic apoB-containing particles) in the arterial wall. Thus, the overall effect of LDL-C level on ASCVD risk is determined by the combination of both plasma levels and time of exposure.<ref>[https://www.sciencedirect.com/science/article/abs/pii/B9780323882866000133 Treatment Guidelines Overview: European Society of Cardiology/European Atherosclerosis Society Guidelines Treatment Guidelines Overview: European Society of Cardiology/European Atherosclerosis Society Guidelines]</ref>}}

LDL particle concentrations drive the majority of atherogenic lipoprotein risk because they represent the majority of all circulating apoB particles. The consensus is to keep ApoB-containing lipoproteins low to reduce atherosclerotic cardiovascular disease risk. 

{{quotebox|An apoB particle is the basic unit of injury to the arterial wall. The more apoB particles within the lumen of the artery, the greater the trapping of apoB particles within the arterial wall, the greater the injury to the arterial wall. The more apoB particles are reduced by therapy, the less the injury to the arterial wall, the greater the opportunity for healing.<ref>[https://pmc.ncbi.nlm.nih.gov/articles/PMC7369156/ Apolipoprotein B Particles and Cardiovascular Disease: A Narrative Review]. pmc.ncbi.nlm.nih.gov.</ref>}}

Cholesterol denialists are either unaware about any of these scientific developments or ignore all of the modern research from clinical trials and human Mendelian randomization studies.

===Lipoprotein (a)===

It is widely accepted in the scientific community that elevated Lipoprotein (a) is an independent risk factor for atherosclerotic cardiovascular disease and stroke.<ref name="acc">[https://www.acc.org/Latest-in-Cardiology/Articles/2023/09/19/10/54/An-Update-on-Lipoprotein-a An Update on Lipoprotein(a): The Latest on Testing, Treatment, and Guideline Recommendations]. acc.org.</ref><ref>[https://pubmed.ncbi.nlm.nih.gov/21500721/ Lipoprotein (a) and risk of cardiovascular disease--a systematic review and meta analysis of prospective studies]. pubmed.ncbi.nlm.nih.gov.</ref><ref>[https://www.ahajournals.org/doi/10.1161/STROKEAHA.106.480657 Lipoprotein (a) and Stroke: A Meta-Analysis of Observational Studies]. ahajournals.org.</ref><ref>[https://www.ahajournals.org/doi/10.1161/ATVBAHA.118.311857 Lipoprotein(a) and Risk of Ischemic Stroke in the REGARDS Study]. ahajournals.org.</ref><ref>[https://www.jacc.org/doi/10.1016/j.jacc.2019.03.524 Elevated Lipoprotein(a) and Risk of Ischemic Stroke]. jacc.org.</ref><ref>[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10531345/ Lipoprotein(a) as a Risk Factor for Cardiovascular Diseases: Pathophysiology and Treatment Perspectives]. ncbi.nlm.nih.gov.</ref><ref>[https://jamanetwork.com/journals/jamacardiology/article-abstract/2792280 Lipoprotein(a) and its Significance in Cardiovascular Disease: A Review]. jamanetwork.com.</ref> LP(a) can increase the risk of developing cardiovascular disease even when LDL-C levels are within the recommended range. Lp(a) levels are to a large extent genetically determined with little influence from environmental or lifestyle factors.<ref name="acc"/><ref>[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471681/ Lipoprotein (a), an independent cardiovascular risk marker]. ncbi.nlm.nih.gov.</ref><ref>[https://www.ahajournals.org/doi/10.1161/ATV.0000000000000147 Lipoprotein(a): A Genetically Determined, Causal, and Prevalent Risk Factor for Atherosclerotic Cardiovascular Disease: A Scientific Statement From the American Heart Association]. ahajournals.org.</ref><ref>[https://www.lipidjournal.com/article/S1933-2874(22)00244-6/fulltext Use of Lipoprotein(a) in clinical practice: A biomarker whose time has come. A scientific statement from the National Lipid Association]. lipidjournal.com.</ref> Typically they do not change after 5 years of age except during times of significant inflammation, liver disease or kidney disease.<ref name="acc"/><ref>[https://www.acc.org/Latest-in-Cardiology/Articles/2019/07/02/08/05/Lipoproteina-in-Clinical-Practice Lipoprotein(a) in Clinical Practice]. acc.org.</ref> It is recommended that LP(a) should be measured in everyone at least once in a lifetime.<ref>[https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehae191/7693374 Eight reasons why lipoprotein(a) should be measured in everyone at least once in a lifetime]. academic.oup.com.</ref>

In 2022, the European Atherosclerosis Society stated:

{{quotebox|Similar to LDL, Lp(a) is an apoB-containing lipoprotein but the number of circulating particles is much lower. Given that risk associated with Lp(a) on a per particle basis may exceed that of LDL, cell signalling effects mediated by Lp(a) rather than Lp(a) accumulation per se may mainly contribute to atherogenicity. Imaging studies revealed that Lp(a) initiates inflammation in the arterial wall, and in advanced coronary artery disease, high Lp(a) levels were associated with accelerated progression of coronary calcium and the necrotic core volume. Similarly in AVS, high Lp(a) and proteins transported by Lp(a) (e.g. autotaxin) induces the expression of inflammatory and calcification genes in valvular interstitial cells and associates with increased incidence and progression of AVS.<ref>[https://academic.oup.com/eurheartj/article/43/39/3925/6670882 Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statemen]. academic.oup.com.</ref>}}

Recently, cholesterol denialists who deny that LDL-C increases cardiovascular disease risk now accept that Lipoprotein (a) increases risk.<ref>For example, [[Paul Saladino]] https://www.youtube.com/watch?v=AYFb9o6kdmQ</ref> This view from cholesterol denialists is contradictory as noted by Alan Flanagan:

{{quotebox|The first thing to note is that Lp(a) contains an LDL particle. Which makes the “Lp(a) is causal but LDL-C isn’t” claim almost absurd from the outset. 

[...]

Burgess et al. (JAMA Cardiology. 2018;3(7): 619-627) conducted a Mendelian randomization analysis involving >80,000 patients and>150,000 controls, where the genetic effect of lower Lp(a) levels was analysed and compared to the effects of lower LDL-C levels.

They demonstrated that the reduction in risk from lowering Lp(a) was proportional to the mass concentration, and that a reduction of 100mg/dL Lp(a) would be required to achieve a meaningful reduction in CHD risk. Now, here is where the rubber hits the road: the magnitude of this 100mg/dL reduction in Lp(a) was similar to the effect of lowering LDL-C by 38mg/dL.

And why is this interesting? Because although their mass concentrations may differ – 100mg for Lp(a) and 38mg for LDL – the cholesterol content of these respective masses is essentially similar: 30-40%.

This in effect tells us what is known: that the transport of cholesterol into the artery, and deposition of cholesterol therein, is the initiating process of atherosclerosis.

Thus, although the mass concentrations between 100mg Lp(a) and 38mg LDL differ, the effect of reducing either by those respective masses is to reduce circulating cholesterol by roughly the same amount. And reduce CHD risk by roughly the same, as a result of lowering the causal exposure.

So for LDL-C denialists to argue that Lp(a) is causal is the most self-defeating cockology ever witnessed.

It is literally them arguing for the exact position – the lipoprotein properties, the mechanism of action, all of it – that they otherwise deny.<ref>[https://www.alineanutrition.com/2020/11/17/lipoproteina-causality-and-checkmate-on-low-carb-cholesterol-denialism/ Lipoprotein(a), Causality, and Checkmate on Low-Carb Cholesterol Denialism]. alineanutrition.com.</ref>}}

Currently there are no approved drug treatments to lower Lp(a). Clinical trials are currently being conducted on Lepodisiran and Muvalaplin.<ref>[https://newsroom.clevelandclinic.org/2023/11/12/trial-shows-a-single-dose-of-an-experimental-therapy-reduces-lipoproteina-an-important-heart-disease-risk-factor-more-than-94-for-nearly-a-year Trial Shows a Single Dose of an Experimental Therapy Reduces Lipoprotein(a), an Important Heart Disease Risk Factor, More than 94% for Nearly a Year]. newsroom.clevelandclinic.org.</ref><ref>[https://www.news-medical.net/news/20230828/First-oral-treatment-for-Lipoprotein(a)-shows-significant-cholesterol-reduction.aspx First oral treatment for Lipoprotein(a) shows significant cholesterol reduction]. news-medical.net.</ref>

===Remnant cholesterol===
[[File:Remnant Cholesterol.png|thumb|200px|Remnant cholesterol and total cholesterol]]
Remnant cholesterol is an atherogenic lipoprotein composed primarily of very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) with chylomicron remnants. It is calculated as total cholesterol minus HDL-C and LDL-C. Elevated remnant cholesterol is associated with increased risk of cardiovascular disease events and stroke.<ref>{{cite journal | author=Nordestgaard BG | title=Triglyceride-Rich Lipoproteins and Atherosclerotic Cardiovascular Disease: New Insights From Epidemiology, Genetics, and Biology | journal= Circulation Research | volume=118 | issue=4 | pages=547–563 | year=2016 | doi= 10.1161/CIRCRESAHA.115.306249 | pmid = 26892957 | doi-access=free }}</ref><ref>{{cite journal|author=Yang XH, Zhang BL, Cheng Y, Fu SK, Jin HM.|year=2023|title=Association of remnant cholesterol with risk of cardiovascular disease events, stroke, and mortality: A systemic review and meta-analysis|journal=Atherosclerosis|url=https://www.sciencedirect.com/science/article/abs/pii/S0021915023001144|volume=371|issue=|pages=21-31| doi=10.1016/j.atherosclerosis.2023.03.012| pmid=36966562}}</ref>

===Total cholesterol===

Total cholesterol also known as serum cholesterol, refers to the overall amount of cholesterol the blood, which is carried by lipoproteins.<ref>[https://www.heartuk.org.uk/cholesterol/understanding-your-cholesterol-test-results- Understand your cholesterol test results]. heartuk.org.uk</ref> It is calculated by summing the HDL level, LDL level, and 20% of the triglyceride level present in a blood sample.<ref>[https://www.heart.org/en/health-topics/cholesterol/about-cholesterol/what-your-cholesterol-levels-mean What Your Cholesterol Levels Mean]. heart.org.</ref><ref>[https://www.medicalnewstoday.com/articles/how-to-calculate-total-cholesterol How to calculate total cholesterol]. medicalnewstoday.com.</ref><ref>[https://www.medicalnewstoday.com/articles/321519 What is serum cholesterol?]. medicalnewstoday.com.</ref> There is a broad consensus that serum cholesterol should be under 200 mg/dl.<ref>[https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/lipid-panel Lipid Panel]. hopkinsmedicine.org.</ref><ref>[https://www.uptodate.com/contents/high-cholesterol-and-lipids-beyond-the-basics Patient education: High cholesterol and lipids (Beyond the Basics)]. uptodate.com.</ref><ref>[https://medlineplus.gov/lab-tests/cholesterol-levels/ Cholesterol Levels]. medlineplus.gov.</ref> There is over 40 years of consistent epidemiological research showing that high serum cholesterol is associated with an increased cardiovascular disease risk in both young and older persons.<ref>[https://pubmed.ncbi.nlm.nih.gov/35886124/ Serum Cholesterol Levels and Risk of Cardiovascular Death: A Systematic Review and a Dose-Response Meta-Analysis of Prospective Cohort Studies]. pubmed.ncbi.nlm.nih.gov.</ref><ref>[https://pubmed.ncbi.nlm.nih.gov/9148647/ Clarifying the direct relation between total cholesterol levels and death from coronary heart disease in older persons]. pubmed.ncbi.nlm.nih.gov.</ref><ref>[https://pubmed.ncbi.nlm.nih.gov/29899019/ Effect of Change in Total Cholesterol Levels on Cardiovascular Disease Among Young Adults]. pubmed.ncbi.nlm.nih.gov</ref><ref>[https://pubmed.ncbi.nlm.nih.gov/12963571/ Lifetime risk of coronary heart disease by cholesterol levels at selected ages]. pubmed.ncbi.nlm.nih.gov.</ref><ref>[https://pubmed.ncbi.nlm.nih.gov/1342260/ Lipids and risk of coronary heart disease. The Framingham Study]. pubmed.ncbi.nlm.nih.gov.</ref><ref>[https://pubmed.ncbi.nlm.nih.gov/32269207/ A Combination of Blood Pressure and Total Cholesterol Increases the Lifetime Risk of Coronary Heart Disease Mortality: EPOCH-JAPAN]. pubmed.ncbi.nlm.nih.gov.</ref><ref>[https://pubmed.ncbi.nlm.nih.gov/2342536/ Ten-year mortality from cardiovascular disease in relation to cholesterol level among men with and without preexisting cardiovascular disease]. pubmed.ncbi.nlm.nih.gov.</ref><ref>[https://pubmed.ncbi.nlm.nih.gov/20117361/ Beyond low-density lipoprotein cholesterol: respective contributions of non-high-density lipoprotein cholesterol levels, triglycerides, and the total cholesterol/high-density lipoprotein cholesterol ratio to coronary heart disease risk in apparently healthy men and women]. pubmed.ncbi.nlm.nih.gov.</ref><ref>[https://pubmed.ncbi.nlm.nih.gov/7596000/ Serum total cholesterol and long-term coronary heart disease mortality in different cultures. Twenty-five-year follow-up of the seven countries study]. pubmed.ncbi.nlm.nih.gov.</ref><ref>[https://pubmed.ncbi.nlm.nih.gov/27016614/ Total cholesterol as a risk factor for coronary heart disease and stroke in women compared with men: A systematic review and meta-analysis]. pubmed.ncbi.nlm.nih.gov.</ref> Recent research supports the lipid hypothesis that lower serum cholesterol is associated with reduced coronary heart disease risk.<ref>[https://www.ahajournals.org/doi/10.1161/JAHA.123.030496 Serum Cholesterol and Impact of Age on Coronary Heart Disease Death in More Than 4 Million Veterans]. ahajournals.org.</ref>

==Other chronic disease risks==

===Dementia risk===

High LDL-C levels are associated with an increased dementia risk.<ref name="alzheimers"/><ref name="dementia"/><ref>[https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(21)00150-1/fulltext Blood cholesterol and risk of dementia in more than 1·8 million people over two decades: a retrospective cohort study]. thelancet.com.</ref><ref>[https://pmc.ncbi.nlm.nih.gov/articles/PMC9993469/ The relationship between midlife dyslipidemia and lifetime incidence of dementia: A systematic review and meta‐analysis of cohort studies]. pmc.ncbi.nlm.nih.gov</ref><ref>[https://lipidworld.biomedcentral.com/articles/10.1186/s12944-024-02032-0 Elevated serum LDL-C increases the risk of Lewy body dementia: a two-sample mendelian randomization study]. lipidworld.biomedcentral.com.</ref> A 2025 study found that LDL-C levels below 70 mg/dL were associated with a 26% reduction in the risk of all-cause dementia and a 28% reduction in the risk of Alzheimer’s disease-related dementia.<ref name="dementia"/><ref>[https://www.theguardian.com/society/2025/apr/01/lowering-bad-cholesterol-may-cut-risk-of-dementia-by-26-study-suggests Lowering bad cholesterol may cut risk of dementia by 26%, study suggests]. theguardian.com.</ref>

===Peripheral Artery Disease===

High LDL-C levels are considered a risk factor for peripheral artery disease.<ref name="ACC">[https://www.acc.org/Latest-in-Cardiology/Articles/2024/08/19/10/45/Lipid-Management-in-Peripheral-Artery-Disease Lipid Management in Peripheral Artery Disease: A Focus on Recent and Evolving Data]. acc.org.</ref><ref>[https://www.sciencedirect.com/science/article/pii/S193328742400206X Association of lipids and lipid-lowering drugs with peripheral arterial disease: A Mendelian randomization study]. sciencedirect.com.</ref> Lipid-lowering medication is recommended to patients with peripheral artery disease.<ref name="ACC"/>

==List of notable cholesterol denialists==
{{collist|4|
*[[Mike Adams]]<ref name="denialism"/>
*[[Eric Berg]]
*[[Leonard Coldwell]]<ref name="denialism"/>
*[[James DiNicolantonio]]
*[[Jason Fung]]
*[[Zoë Harcombe]]
*[[Malcolm Kendrick]]<ref name="denialism"/>
*[[Chris Kresser]]
*[[Abd ul-Rahman Lomax]]
*[[Dwight Lundell]]
*[[Aseem Malhotra]]<ref name="The Guardian"/>
*[[Joseph Mercola]]<ref name="denialism"/>
*[[Jimmy Moore]]
*[[Tom Naughton]]
*[[Tim Noakes]]<ref>[https://www.health24.com/Medical/Heart/Foods-diet-and-your-heart/Tim-Noakes-called-a-cholesterol-denialist-20130210 Tim Noakes called a 'cholesterol denialist']</ref>
*[[David Perlmutter]]
*[[Ray Peat]]
*[[Matthias Rath]]
*[[Uffe Ravnskov]]<ref name="The Guardian"/>
*[[Marika Sboros]]
*[[Gary Taubes]]
*[[Paul Saladino]]
*Nina Teicholz 
*Frank Mitloehner
}}

==See also==

*[[Saturated fat and cardiovascular disease]]
*[[Dietary cholesterol]]
*[[Institute for Natural Healing]]
*[[Vaccine denialism]]

==External links==

*[https://www.youtube.com/watch?v=ZBgDa2Vg9H8 LDL Particle Size - Does Size Matter? Cardiologist Explains]
*[https://sigmanutrition.com/cholesterol-mortality/ Low Cholesterol & Increased Mortality Risk?: Clarifying the Confusion]

==References==
{{reflist|2|80%}}

[[Category:Cholesterol and statin denialists| ]]
[[Category:Denialism]]

Categories: Cholesterol and statin denialists, Denialism