Challenging the Cholesterol Hypothesis: What Key Studies Reveal About Heart Disease, Cholesterol Levels, and Statin Drugs by Jeffrey Dach MD (Part Four)
For decades, mainstream cardiology believed the cholesterol theory of heart disease. This is the theory that high serum cholesterol, especially the low-density lipoprotein (LDL) subfraction (also called the “bad” cholesterol), is what causes coronary artery disease, namely causes heart attacks and strokes by building up a cholesterol layer inside the wall of the artery which ultimately clogs the artery and blocks blood flow.
Header Image: CAT scan showing hemorrhagic stroke. Source: Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013. Author: OpenStax College, CC 3.0. Link to attribution on Wikimedia Commons.
The Cholesterol Theory of Heart Disease
The cholesterol theory of atherosclerotic vascular disease is the basis for dietary advice to cut saturated fat and the widespread prescription of statin drugs to aggressively lower cholesterol. Yet several rigorous studies and re-analyses of older trials have produced discordant results that disprove the cholesterol theory. Below, we examine these major studies, and what they suggest about the cholesterol theory and the use of statin drugs.
Minnesota Coronary Experiment Re-Analysis
14% reduction in Cholesterol
In 2016, Dr. Christopher Ramsden re-analyzed data from the Minnesota Coronary Experiment, a large randomized controlled trial originally conducted between 1968 and 1973. Participants were assigned either a diet high in saturated fat or a diet that replaced much of that saturated fat with vegetable oils rich in linoleic acid (an omega-6 polyunsaturated fat). The vegetable-oil diet successfully lowered participants’ total blood cholesterol by an average of about 14 percent. However, this reduction did not translate into fewer deaths or less heart disease. Instead, the researchers found that for every 30 mg/dL drop in serum cholesterol, the risk of death from any cause rose by 22 percent.
Autopsy Data
Autopsy data also showed no reduction in artery plaque or heart attacks in the lower-cholesterol group. These results challenge the core prediction of the cholesterol theory: that lowering cholesterol through diet should reduce cardiovascular disease and extend life. They also raise questions about statin drugs, which are prescribed precisely to achieve similar or greater cholesterol reductions, by showing that cholesterol lowering itself has no survival benefit, instead it is linked to higher overall mortality. [1]
Sydney Diet Heart Study Re-Analysis
62% higher all cause mortality
In 2013, Dr. Christopher Ramsden recovered previously unpublished data from the Sydney Diet Heart Study, a randomized trial run from 1966 to 1973 in men who had already experienced a coronary event. One group replaced saturated fats with safflower oil and margarine high in linoleic acid, a common vegetable-oil, while the control group continued their usual diet. Cholesterol levels fell in the intervention group as expected, yet the men eating the high-vegetable-oil diet experienced higher rates of death—approximately 62 percent higher all-cause mortality and 70 percent higher cardiovascular and coronary heart disease mortality compared with controls. When these recovered results were added to a broader meta-analysis of similar linoleic-acid trials, there was still no evidence of benefit and a signal of possible harm. This finding directly counters the cholesterol theory’s assumption that lowering cholesterol (via polyunsaturated vegetable oils) will protect the heart. It also has implications for statin therapy: if lowering serum cholesterol with dietary modification increases mortality, then this brings into question the mainstream medicine practice of prescribing statin drugs to reduce serum cholesterol. [2]
Swedish AMORIS Cohort Study on Centenarians
In 2023-2024, Dr. Shunsuke Murata and colleagues examined blood samples collected years earlier from participants in the large Swedish AMORIS cohort and followed them for up to 35 years to see who reached age 100. Higher total cholesterol levels earlier in life were associated with a greater likelihood of becoming a centenarian, while very low levels of cholesterol (along with higher glucose, creatinine, and certain liver enzymes) were linked to a lower chance of extreme longevity. A later correction clarified that the absolute difference in cholesterol between those who reached 100 and those who did not was small, and that high cholesterol neither strongly increased nor decreased the odds once other factors were considered. Still, the overall pattern, that people who lived the longest tended not to have the lowest cholesterol, directly opposes the cholesterol theory, that lower the cholesterol, the better for long-term health. For the cholesterol theory and statin prescribing, especially in older adults, this indicates that aggressively lowering cholesterol to very low levels is not healthy and does not promote longevity. [3]
Systematic Review of LDL Cholesterol and Mortality in the Elderly
In 2016, Dr. Uffe Ravnskov conducted a systematic review of 19 cohort studies involving more than 68,000 people aged 60 and older. In the large majority of these studies (covering about 92 percent of participants), higher LDL cholesterol was either associated with lower all-cause mortality or showed no association with increased death risk.
In other words, elderly people with higher “bad” cholesterol often lived as long as or longer than those with lower levels. This inverse or neutral relationship is difficult to reconcile with the cholesterol theory’s claim that elevated LDL is inherently harmful and should be lowered throughout life. It also prompts caution about routine statin use in older adults without established heart disease: if higher LDL is not linked to shorter lifespan in this age group, there is no medical justification for lowering cholesterol with statin drugs solely. [4]
Studies Linking Very Low LDL Cholesterol to Hemorrhagic Stroke Risk
Multiple prospective studies, including a large 2019 analysis by Dr. Chaoran Ma of 96,000 Chinese adults followed for nine years, have examined the relationship between very low LDL cholesterol and bleeding strokes, also called intracerebral hemorrhage. Participants with LDL levels below 70 mg/dL showed elevated risk compared with those in the 70–99 mg/dL range; the risk was roughly 65 percent higher for levels of 50–69 mg/dL and approached a near-tripling (hazard ratio about 2.69) for levels under 50 mg/dL. Other cohort data have reported similar patterns, especially when hypertension is also present. While lowering LDL clearly reduces ischemic (clot-related) events in high-risk patients, these findings indicate a potential trade-off: driving LDL extremely low may increase the chance of dangerous brain bleeds. This finding challenges cholesterol theory that treats lowering LDL cholesterol with statin drugs as safe. Obviously, it is not safe because is causes increased hemorrhagic strokes. [5]
Conclusion: Lowering cholesterol does not automatically equate to longer life or reduced all cause mortality. Higher cholesterol levels are associated with improved survival, and very low levels carry their own risks of increased hemorrhagic stroke. Patients and clinicians can use these studies to have more nuanced conversations about diet, individual risk, and to justify completely avoiding the adverse effects of lowering serum cholesterol with statin drugs.
Heart Book: How to Keep Your Heart Healthy by Jeffrey Dach MD
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Heart Book is a journey through the confusing maze of literature on coronary artery disease, the number-one killer in America. With his years of practice in vascular radiology, Dr. Dach has the background, credentials, and experience to transform your understanding of heart disease. The old medical paradigms have been upended, yet mainstream cardiology clings to these tired dogmas as if nothing has changed. Be prepared to be shocked, amazed, provoked, and gratified as this book empowers you to take control of your own heart health.
Articles with Related Interest:
Atherosclerotic Plaque and Infection Part Two
The Failure of Cholesterol Lowering Drugs
Coronary Artery Disease: Questions and Answers
Does Cholesterol Cause Coronary Artery Disease ?
Calcium Score Determines Who to Treat with Statin Drug
Calcium Score Diabetes and Statin Drugs
Plant Based Diet, Health Benefits for Coronary Artery Disease
LDL-Cholesterol Does Not Cause Coronary Artery Disease
Low Level Endotoxemia, Depression, Endocrinopathy and Coronary Artery Disease
Fibrinolytic Enzymes, Nattokinase, Lumbrokinase Prevent and Reverse Atherosckerosis
Reverse Heart Disease with Coronary Calcium Score
Low Level Endotoxemia LPS Theory of Coronary Artery Disease
Calcium Score Paradigm Shift in Cardiology
Coronary Calcium Score Benefits of Aged Garlic
The Art of the Curb Side Cholesterol Consult
Cholesterol and Atherosclerosis:Autopsy Studies Show No Correlation
Statin Denialism Internet Cult with Deadly Consequences
Defending the Cholesterol Hypothesis in the Elderly
Does High Cholesterol Cause Heart Disease ?
Familial Hypercholesterolemia and Statin Drugs
Donating Blood Prevents Heart Disease
Does Cholesterol Cause Heart Disease ? Part two
Atherosclerotic Plaque as Infected Biofilm on Electron Microscopy
Coronary Calcium Score Paradigm Shift Podcast
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Heart Book by Jeffrey Dach MD
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www.drdach.com
References
1. Ramsden, Christopher E., et al. “Re-evaluation of the Traditional Diet-Heart Hypothesis: Analysis of Recovered Data from Minnesota Coronary Experiment (1968-73).” *BMJ*, vol. 353, 2016, p. i1246. https://doi.org/10.1136/bmj.i1246.
2. Ramsden, Christopher E., et al. “Use of Dietary Linoleic Acid for Secondary Prevention of Coronary Heart Disease and Death: Evaluation of Recovered Data from the Sydney Diet Heart Study and Updated Meta-Analysis.” *BMJ*, vol. 346, 2013, p. e8707. https://doi.org/10.1136/bmj.e8707.
3. Murata, Shunsuke, et al. “Blood Biomarker Profiles and Exceptional Longevity: Comparison of Centenarians and Non-Centenarians in a 35-Year Follow-Up of the Swedish AMORIS Cohort.” *GeroScience*, vol. 46, no. 2, 2024, pp. 1693–1702. https://doi.org/10.1007/s11357-023-00936-w.
4. Ravnskov, Uffe, et al. “Lack of an Association or an Inverse Association between Low-Density-Lipoprotein Cholesterol and Mortality in the Elderly: A Systematic Review.” *BMJ Open*, vol. 6, no. 6, 2016, p. e010401. https://doi.org/10.1136/bmjopen-2015-010401.
5. Ma, Chaoran, et al. “Low-Density Lipoprotein Cholesterol and Risk of Intracerebral Hemorrhage: A Prospective Study.” *Neurology*, vol. 93, no. 5, 2019, pp. e445–e457. https://doi.org/10.1212/WNL.0000000000007853.
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Kinked Side Chain
Oils rich in linoleic acid are not trans fats. Linoleic acid is a naturally occurring omega-6 polyunsaturated fatty acid (PUFA). It has two double bonds in the cis configuration (the hydrogen atoms sit on the same side of the carbon chain, creating a kinked shape). This makes pure linoleic-acid–rich oils—such as high-linoleic safflower, sunflower, corn, and soybean oils—liquid at room temperature and chemically distinct from trans fats.
Straight Side Chain
Trans fats: Unsaturated fatty acids that contain at least one double bond in the trans configuration (hydrogen atoms on opposite sides of the chain). This produces a straighter molecule that behaves more like a saturated fat.
Healthy unsaturated fats (including linoleic acid): Almost all natural plant and fish oils have cis double bonds.
Monounsaturated fats (e.g., oleic acid in olive oil) have one cis double bond; polyunsaturated fats such as linoleic acid (omega-6) and alpha-linolenic acid (omega-3) have two or more cis double bonds.
Industrial trans fats: Created by partial hydrogenation of vegetable oils (turning liquid oils into semi-solid fats for margarine, shortening, fried foods, and baked goods). Small amounts also occur naturally in the fat of ruminant animals (cows, sheep).
Linoleic acid and other healthy fats: Found in unhydrogenated vegetable oils (safflower, sunflower, corn, soybean), nuts, seeds, avocados, olive oil (mainly monounsaturated), and fatty fish (omega-3s). Pure oils rich in linoleic acid contain essentially zero industrial trans fat unless they have been deliberately partially hydrogenated.
Health effects Trans fats: Raise LDL (“bad”) cholesterol, lower HDL (“good”) cholesterol, promote inflammation, and increase risk of coronary heart disease, cardiovascular death, and all-cause mortality. Both industrial and ruminant trans fats are considered harmful; major health organizations recommend keeping intake as low as possible (ideally <1% of energy).
Healthy unsaturated fats (cis monounsaturated and polyunsaturated, including linoleic acid): When they replace saturated fat or trans fat, they generally lower LDL cholesterol and are associated with reduced cardiovascular risk in many observational studies and some trials. Linoleic acid is an essential fatty acid (the body cannot make it). Very high intakes of omega-6 relative to omega-3 remain a topic of scientific discussion, but the fatty acid itself is not classified as a trans fat and is not considered inherently harmful in the same way.
In the older dietary trials (such as the Sydney Diet Heart Study and Minnesota Coronary Experiment), researchers increased linoleic acid mainly by using safflower oil or similar vegetable oils. Some of the margarines used in that era also contained industrial trans fats produced by partial hydrogenation; modern analyses try to distinguish the effects of the linoleic acid itself from any accompanying trans fat.
Mozaffarian, Dariush, Alberto Aro, and Walter C. Willett. “Health Effects of Trans-Fatty Acids: Experimental and Observational Evidence.” European Journal of Clinical Nutrition, vol. 63, Suppl. 2, 2009, pp. S5–S21. https://doi.org/10.1038/sj.ejcn.1602973.
(Highly cited review summarizing controlled trials and cohort studies showing the adverse effects of industrial trans fats on blood lipids and coronary heart disease risk.)
World Health Organization. “Trans Fat.” WHO Fact Sheet, 24 January 2024. https://www.who.int/news-room/fact-sheets/detail/trans-fat.
(Authoritative summary defining trans fats, documenting their global health burden, and recommending near-elimination of industrially produced trans fat while distinguishing them from natural cis-unsaturated oils.)
Harvard T.H. Chan School of Public Health. “Types of Fat.” The Nutrition Source. https://www.hsph.harvard.edu/nutritionsource/what-should-you-eat/fats-and-cholesterol/types-of-fat/.
(Clear, evidence-based overview of saturated, monounsaturated, polyunsaturated (including linoleic acid), and trans fats, with practical food sources and health implications.)
Jeffrey Dach MD
7450 Griffin Road, Suite 190
Davie, Fl 33314
954-792-4663
my web site: https://drjeffreydachmd.com/
my personal blog: www.jeffreydachmd.com
Bioidentical Hormones 101 Second Edition
Menopausal Hormone Replacement, Health Benefits
Natural Thyroid Toolkit by Jeffrey Dach MD
Cracking Cancer Toolkit ebook
Cracking Cancer Toolkit print version
Heart Book by Jeffrey Dach MD
www.naturalmedicine101.com
www.bioidenticalhormones101.com
www.truemedmd.com
www.drdach.com
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