Vinegar/Acetate Protects Your Blood Vessels Activating Antioxidant Protection.

I’ve discussed the inner lining of blood vessels — the endothelium — several times before. Virtually all studies conclude that oxidative stress causes metabolic and functional changes in these critically important cells that protect your vasculature. We already know that turbulent blood flow in vessel branches and bends triggers oxidative stress. That stress can also cause cellular senescence and reduce adaptability to changing conditions. This impairs oxygen and nutrient delivery and blocks angiogenesis — the formation of new blood vessels. Vasodilation — the ability of vessels to expand based on tissue needs — also stops working. Maintaining functional vascular endothelium is therefore vital.

Let’s look at a study that examined endothelial cells in two states: a seemingly quiescent one where cells are just working, and a proliferative one where new blood vessels form. The quiescent state is different from cellular senescence, though they may appear similar. Quiescent endothelial cells (QEC) are active, relying on oxidative phosphorylation for ATP energy production — primarily using fats, much more than glucose. This was also observed in studies on cellular senescence. Interestingly, acetate was used there to help resolve issues by supporting fat metabolism. If fat oxidation is impaired, endothelial cells switch to anaerobic metabolism — fermenting glucose into lactate. While this lowers production of superoxide and hydrogen peroxide during glucose energy conversion, it sacrifices strong antioxidant protection. This can trigger inflammation, senescence, or the construction of new structures — if cells aren’t yet senescent.

Comparison of endothelial cell metabolism in the quiescent state (QEC) versus the proliferative state (PEC), beta oxidation of fats, glycolysis, glucose oxidation, glutamate oxidation, fat synthesis, expression of long-chain fat transporter CPT1A into mitochondria, under stress from turbulent flow (shear stress).

Why is fat metabolism so crucial to endothelial health? Because it supports antioxidant defenses. Research shows fats entering mitochondria fuel the regeneration of NADPH molecules, which are essential to produce glutathione (GSH), the body’s main cellular antioxidant. Without this protection, fats can't be safely burned. Although glucose metabolism also regenerates NADPH through the PPP pathway, it's insufficient during fat oxidation. So mitochondrial sources must be activated: enzymes IDH2, ME3, and NNT.

What happens when the mitochondrial enzymes IDH2 and ME3—responsible for NADPH regeneration—are disabled, or when fat entry into mitochondria is blocked (CPT1A KD)? Antioxidant defenses are lost, leading to increased oxidized glutathione. 

If fat oxidation is hindered — for example, by blocking fat entry into mitochondria via CPT1A KD — antioxidant protection weakens and cells become vulnerable. Oxidative stress may trigger cellular senescence. Short- and medium-chain fats (up to 12 carbons) bypass CPT1A to enter mitochondria, making them helpful when transport via CPT1A is disrupted.

It’s also important to note that fructose, through activation of the KHK enzyme, acetylates and degrades CPT1A — limiting long-chain fat oxidation and promoting storage in fat tissue or the liver. So be carefull with your fruit and sugar intake.

Sodium acetate/vinegar protects the endothelial lining from oxidative stress caused by suppressed long-chain fat metabolism (CPT1A KD), hydrogen peroxide (H₂O₂), or endotoxins (LPS). 

Fat metabolism is essential for antioxidant protection. How exactly does acetate activate it? The pathway is complex and not fully understood. Other studies suggest it works through acetylation and deacetylation of various proteins, likely involving acetylation of LKB1, activation of SIRT1 deacetylase, AMPK activation, ACC phosphorylation, UCP2 activation, and more. It’s complicated. But even without fully grasping it, we know it works.

Acetate works via the enzyme ACSS1, which converts acetate into acetyl-CoA molecules. Disabling ACSS1 eliminates acetate's protective effect.


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References:

Quiescent Endothelial Cells Upregulate Fatty Acid β-Oxidation for Vasculoprotection via Redox Homeostasis


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