The Best Vitality & Health Protocols | Dr. Rhonda Patrick

When LPS binds to the apoB protein on small dense LDL particles, hepatic LDL receptor recognition is obscured, preventing normal liver clearance and causing arterial wall entrapment and foam cell formation by macrophages.

"And so when it's time to get recycled back into the liver, what do you know? The apoB protein's obscured by that LPS and it's not recycled. And so it gets lodged into the arterial wall. And because there's an LPS bound to this small dense LDL particle, macrophages... tries to engulf it, but it can't cuz it's not bacteria, and you get the macrophage stuck to that lipoprotein-LPS complex and you get the formation of a foam cell." (said at 0:46:15)

The speaker's proposed mechanism is contradicted by physiological and mechanistic evidence on lipoprotein-endotoxin clearance and foam cell biology. First, pathogen lipids like lipopolysaccharide (LPS) transferred to apoB-containing lipoproteins (including LDL) do not obscure hepatic receptor recognition to block clearance; rather, the LDL receptor (LDLR) pathway is a primary physiological mechanism by which circulating LPS bound to apoB lipoproteins is cleared by hepatocytes and excreted into bile. Second, macrophage foam cell formation does not occur because macrophages fail to engulf LDL particles and get 'stuck'; rather, macrophages actively internalize modified lipoproteins (such as oxidized LDL) via scavenger receptors (e.g., CD36, SR-A) faster than cholesterol can be effluxed, accumulating intracellular lipid droplets to become foam cells.

• contradicts: The Central Role of Proprotein Convertase Subtilisin/Kexin Type 9 in Septic Pathogen Lipid… (American journal of respiratory and critical care medicine 2015) · cited 60x in the literature

  "Next, LPS binding protein, phospholipid transfer protein, and other transfer proteins transfer these lipids to ApoB-containing lipoproteins, including low-density (LDL) and very-low-density lipoproteins and chylomicrons. Pathogen lipids within these lipoproteins and their remnants are then cleared from the circulation by the liver. Hepatic clearance involves the LDL receptor (LDLR) and possibly other receptors." (abstract, results, passage verified)

  pubmedfull study (doi)

Chronic negative stress increases glucocorticoid receptor density and decreases mineralocorticoid receptor density, unlike hormetic stressors.

"So, if you if you look at what activates cortisol in a negative way: chronic stress, let's say emotional, financial, psychological; chronic sleep deprivation; like that bad type of stress, you're not getting a big spike, you're getting a slow drip of it. And so, what happens is when you have that type of stress, you're increasing the glucocorticoid receptors, and you're decreasing the mineralocorticoid receptors." (said at 1:05:48)

The speaker claims that chronic negative stress increases glucocorticoid receptors (GRs) and decreases mineralocorticoid receptors (MRs). The direction of effect for glucocorticoid receptors is inverted: extensive neurobiological research shows that chronic stress and prolonged glucocorticoid elevation downregulate or desensitize glucocorticoid receptors (GRs) in key brain regions like the hippocampus and prefrontal cortex, impairing negative feedback regulation of the hypothalamic-pituitary-adrenal (HPA) axis. While chronic stress does downregulate MRs (as stated in the second part of the claim), asserting that chronic negative stress increases GR density contradicts established findings.

• contradicts: Stress regulation of adrenocorticosteroid receptor gene transcription and mRNA expression … (Brain research. Molecular brain research 2000) · cited 117x in the literature

  "Chronic stress exposure down-regulated GR mRNA in CA3 only; effects were first evident 7 days post stress and persisted for the entire stress time-course (28 days)." (abstract, results, passage verified)

  pubmedfull study (doi)
• contradicts: Influence of chronic stress on brain corticosteroid receptors and HPA axis activity. (Pharmacological reports : PR 2013) · cited 111x in the literature

  "Disruption of the glucocorticoid negative feedback system evoked in animals by chronic stress can be induced by downregulation of glucocorticoid receptors (GRs) in several brain regions." (abstract, results, passage verified)

  pubmedfull study (doi)
• partial: Stress and Depression: a Crucial Role of the Mineralocorticoid Receptor. (Journal of neuroendocrinology 2016) · cited 182x in the literature

  "Limbic MR is down-regulated by chronic stress and during depression but induced by antidepressants." (abstract, results, passage verified)

  pubmedfull study (doi)