Cholesterol & Inflammation: Friend or Foe?
The debate over cholesterol’s role in cardiovascular disease has been ongoing for decades, with LDL often labeled as "bad cholesterol." However, emerging research suggests that LDL plays a protective role against lipopolysaccharides (LPS), a toxic endotoxins released by gram-negative bacteria in the gut.
Rather than being a direct cause of cardiovascular disease, high LDL levels may sometimes indicate a immune response to chronic endotoxemia and systemic inflammation
What is LPS and How Does it Relate to Cholesterol?
Lipopolysaccharides (LPS) are toxic components found in the outer membrane of gram-negative bacteria like E. coli and Klebsiella. When gut integrity is compromised due to leaky gut, dysbiosis, or infection, LPS can enter the bloodstream, triggering systemic inflammation and immune activation.
Research Findings on LPS & Cholesterol:
LDL binds to LPS to neutralize its harmful effects.
Source: Ravnskov U. High cholesterol may protect against infections and atherosclerosis. Q J Med. 2013; 96:927-934.
60% of LPS in circulation is bound to HDL, with additional binding to LDL.
Source: Page MJ, Kell DB, Pretorius E. The Role of Lipopolysaccharide-Induced Cell Signalling in Chronic Inflammation. Chronic Stress. 2022; Volume 6:1-18.
Lipoproteins, including LDL, inactivate microbial toxins and prevent excessive immune stimulation.
Source: Journal of Atherosclerosis and Thrombosis, Vol. 19, No. 10.
Why Does LDL Increase in Chronic Illness?
When LPS enters the bloodstream, the body releases lipoproteins (LDL, HDL, chylomicrons) to bind to the endotoxins. This binding prevents LPS from activating inflammatory cytokines (TNF-α, IL-6), which would otherwise contribute to chronic inflammation and tissue damage.
Additionally, LPS can cause metabolic dysfunction, leading to elevated cholesterol as a secondary response. Some key mechanisms include:
LPS-induced cytokine release increases lipid mobilization.
LPS disrupts mitochondrial function, reducing energy metabolism and increasing oxidative stress.
LPS lowers thyroid hormones, contributing to reduced cholesterol clearance.
Gut-derived endotoxins impair liver detoxification, leading to dysregulated lipid metabolism.
Key Biomarkers to Assess Cardiovascular Risk vs. Protective LDL Response
Instead of relying solely on LDL levels, a functional approach to cardiovascular risk assessment should include:
Oxidized LDL – Determines whether LDL is being damaged and contributing to plaque formation.
High-Sensitivity CRP (hs-CRP) – Identifies systemic inflammation levels.
Myeloperoxidase (MPO) – Assesses oxidative stress and vascular inflammation.
Lipoprotein Phospholipase A2 (Lp-PLA2) – Measures unstable plaque activity.
Homocysteine – Evaluates endothelial function and cardiovascular stress.
Fasting Insulin & Glucose – Determines metabolic health and risk for insulin resistance.
C-Peptide – Assesses pancreatic function and insulin secretion.
Coronary Artery Calcium Score – Evaluates arterial calcification, a stronger predictor of heart disease than LDL alone.
Addressing the Root Cause: Gut Health & Detoxification
If elevated LDL is a response to chronic LPS exposure, reducing gut inflammation, improving bile acid function, and restoring metabolic balance should be the priority. Strategies include:
1. Supporting Gut Integrity
Increase butyrate-producing probiotics (Bifidobacterium, Akkermansia) to strengthen the gut lining.
Use colostrum or L-glutamine to repair intestinal permeability.
2. Enhancing Bile Flow & Liver Detoxification
Taurine and glycine support bile acid conjugation, aiding in LPS clearance.
Beef tallow & coconut oil help neutralize endotoxins and reduce oxidative stress.
3. Avoiding Pro-Inflammatory Foods
Fructose, alcohol, and polyunsaturated fats (PUFAs) increase oxidative stress and worsen LPS effects.
Saturated fats (like coconut oil) are more protective against endotoxin-induced inflammation.
The Role of Advanced Testing: GI MAP & OAT Testing for Endotoxemia
To determine if LPS and endotoxemia are driving high cholesterol, I recommend advanced gut testing:
GI MAP Test – Evaluates gut dysbiosis, bacterial overgrowth, and markers of leaky gut.
Organic Acids Test (OAT) – Identifies gut-derived toxins, mitochondrial dysfunction, and metabolic imbalances.
Zonulin Levels – Assesses intestinal permeability and its impact on systemic inflammation.
Leaky gut syndrome is a biological process triggered by toxins, autoimmune conditions, celiac disease, and infections. Zonulin, a protein in the digestive system, regulates tight junctions between gut cells. Chronic inflammation increases zonulin, potentially opening up the blood-brain barrier and contributing to neuroinflammation in conditions like multiple sclerosis (MS).
The Lymphatic System’s Role in Cardiovascular & Gut Health
The lymphatic system is essential for reducing systemic inflammation. Lymphatic vessels serve as the communication network for immune cells, aiding in the clearance of metabolic waste, toxins, and immune mediators. The gut-associated lymphoid tissue (GALT) plays a key role in immune function and lipid metabolism.
Cholesterol: A Multi-Functional Molecule
Cell Membranes – Cholesterol constitutes 25–30% of lipid membranes, modulating fluidity and receptor function.
Oxysterols – Modulate immune function and inflammation.
Bile Acids – Aid in fat digestion, detoxification, and cholesterol homeostasis.
Hormonal Precursor – Cholesterol is essential for cortisol, estrogen, testosterone, and vitamin D synthesis.
Rethinking Cholesterol in Chronic Illness
Rather than immediately lowering cholesterol with statins, it’s essential to investigate whether LPS and systemic inflammation are the root cause of elevated lipids. Addressing gut health, mitochondrial function, and oxidative stress should be the priority in managing cardiovascular risk, rather than focusing solely on LDL levels.
If you're struggling with high cholesterol and want a functional approach to heart health, schedule a consultation to uncover the root cause of your metabolic and cardiovascular health concerns.
