The Clot Thickens

1. The cholesterol hypothesis of heart disease is fundamentally flawed

"The diet-heart hypothesis, like any hypothesis, has to rest on a basic understanding of the science underlying it. In this case it came into being purely through the process of reverse engineering."

Flawed foundations. The cholesterol hypothesis was built on misinterpreted evidence and flawed studies. LDL cholesterol does not simply "leak" into artery walls, as the endothelium forms a tight barrier. Many populations with high cholesterol levels have low rates of heart disease, and vice versa.

Misguided focus. Decades of research and billions of dollars have been spent trying to lower cholesterol levels, with minimal impact on cardiovascular disease rates. This misguided focus has diverted attention and resources from more significant risk factors and potential interventions.

Industry influence. The pharmaceutical and food industries have heavily promoted the cholesterol hypothesis to sell statins and low-fat foods. This has created a powerful financial incentive to maintain the status quo, despite mounting evidence against it.

2. Atherosclerosis is caused by blood clots, not cholesterol buildup

"Thromboembolic material is therefore sufficient on its own to induce plaque formation."

Clot formation. When the endothelium is damaged, blood clots form to cover the injured area. These clots can then be incorporated into the artery wall, forming the basis of atherosclerotic plaques.

Plaque composition. Atherosclerotic plaques contain fibrin, platelets, red blood cells, and other components of blood clots. The cholesterol found in plaques likely comes from red blood cells, not LDL particles.

Historical evidence. Early researchers like Karl von Rokitansky proposed the "encrustation hypothesis" in the 1850s, suggesting that plaques were the result of blood clots. This idea was largely forgotten as the cholesterol hypothesis gained dominance.

3. Endothelial damage and dysfunction are at the root of cardiovascular disease

"The endothelium, with its diversity of physiological functions is a main target of bacterial toxins."

Endothelial barrier. The endothelium forms a critical barrier between the bloodstream and artery walls. Damage to this barrier is the first step in atherosclerosis development.

Protective glycocalyx. The glycocalyx, a gel-like layer covering endothelial cells, plays a crucial role in protecting the endothelium. Factors that damage or strip away the glycocalyx increase CVD risk.

Nitric oxide production. Healthy endothelial cells produce nitric oxide, which has numerous protective effects:

• Dilates blood vessels
• Prevents blood clot formation
• Reduces inflammation
• Inhibits smooth muscle cell proliferation

4. Psychological stress and HPA axis dysfunction significantly increase CVD risk

"Upwards of 40-60% of depressed patients experience hypercortisolemia [high blood cortisol levels] or other disturbances of the HPA system."

Chronic stress impact. Prolonged psychological stress dysregulates the hypothalamic-pituitary-adrenal (HPA) axis, leading to:

• Elevated cortisol levels
• Insulin resistance
• Endothelial dysfunction
• Increased inflammation

Mental health connection. Conditions like depression, anxiety, and PTSD are associated with significantly increased CVD risk, often mediated through HPA axis dysfunction.

Social factors. Socioeconomic status, social isolation, and lack of support networks contribute to chronic stress and increased CVD risk. This helps explain population-level disparities in cardiovascular health.

5. Diabetes and insulin resistance are major drivers of cardiovascular disease

"Insulin resistance is closely linked to essential hypertension."

Metabolic dysfunction. Insulin resistance and diabetes cause multiple harmful effects:

• Endothelial damage
• Increased inflammation
• Dysregulation of blood sugar levels
• Hypertension
• Dyslipidemia

Glucose toxicity. Chronically elevated blood glucose levels directly damage the endothelium and glycocalyx, accelerating atherosclerosis development.

Lifestyle interventions. Low-carbohydrate diets and high-intensity interval training can effectively reverse insulin resistance and improve cardiovascular health in many cases.

6. Environmental factors like air pollution contribute to endothelial damage

"There is a proven link between exposure to traffic-derived particulate air pollution and the incidence of platelet-driven cardiovascular diseases."

Nanoparticle damage. Tiny particles from air pollution can cross the lung-blood barrier and directly damage the endothelium throughout the body.

Historical impact. Improvements in air quality have likely contributed significantly to declining CVD rates in many countries over the past decades.

Occupational hazards. Certain professions with high exposure to air pollution or other toxic substances (e.g., miners, industrial workers) have elevated CVD risk.

7. Lifestyle choices can protect the endothelium and reduce CVD risk

"The body is exceptionally good at keeping the level of all substances that float about in the bloodstream under tight control."

Dietary choices. Consuming a diet rich in:

• Vegetables and fruits
• Healthy fats (e.g., olive oil, avocados)
• Adequate protein
• Limited refined carbohydrates
  Can support endothelial health and reduce inflammation.

Exercise benefits. Regular physical activity, especially high-intensity interval training, improves endothelial function, insulin sensitivity, and overall cardiovascular health.

Stress management. Practices like meditation, deep breathing, and maintaining strong social connections can help regulate the HPA axis and reduce CVD risk.

8. Certain supplements and therapies may offer cardiovascular benefits

"Vitamin C deficiency results in impaired immunity and higher susceptibility to infections. In turn, infections significantly impact on vitamin C levels due to enhanced inflammation and metabolic requirements."

Key supplements. Several supplements have shown promise in supporting cardiovascular health:

• Vitamin C
• Vitamin D
• Magnesium
• Coenzyme Q10
• L-arginine/L-citrulline

Controversial therapies. Some unconventional treatments, such as chelation therapy, have shown potential benefits in clinical trials, though more research is needed.

Personalized approach. The effectiveness of supplements and therapies may vary based on individual risk factors and health status.

9. Socioeconomic factors play a crucial role in cardiovascular health

"An estimated 4,000 Israelis die in an average year due to an inadequate amount of magnesium in their bodies – and the amount they get from natural potable water sources is increasingly declining due to the growing desalination of sea water."

Health disparities. Socioeconomic status is strongly correlated with CVD risk, influenced by factors such as:

• Access to healthcare
• Diet quality
• Environmental exposures
• Chronic stress levels
• Education about health risks

Population-level interventions. Addressing CVD risk requires considering broader societal factors beyond individual lifestyle choices.

Global patterns. The rise and fall of CVD rates in different countries often correlate with socioeconomic changes and public health measures.

Last updated: March 3, 2025