Tag Archives: lipid oxidation

Why measuring oxidized LDL (lipid peroxides) is important

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Cholesterol is the precursor for all steroid hormones and a constituent of every cell membrane, but it participates in cardiovascular diseases (in which blood vessels are damaged by inflammation) when it becomes damaged by oxidation. A paper just published in the Journal of Vascular Research elucidates the molecular mechanisms by which oxidized LDL damages blood vessels. Specifically, the authors…

“…tested the hypothesis that oxidized low-density lipoprotein (oxLDL)-induced inactivation of Akt within endothelial progenitor cells (EPCs) is mediated at the level of Phosphoinositide 3-kinase (PI3K), specifically by nitrosylation of the p85 subunit of PI3K, and that this action is critical in provoking oxLDL-induced EPC apoptosis.”

Endothelial progenitor cells play a critical role in repair of blood vessel walls. When their function is impaired there is a much greater risk of cardiovascular disease. EPC apoptosis is the death of these important cells. Akt is a kinase ‘signaling molecule’ that prevents apoptosis. Additionally, the PI3K pathway is necessary for normal blood vessel function through endothelial nitric oxide synthase (eNOS) which produces the beneficial nitric oxide that instigates blood vessel relaxation, endothelial growth and repair. When oxidized LDL (oxLDL) is taken up by EPCs they are subject to oxidative stress that impairs their survival. Specifically what did they find when EPCs were exposed to oxLDL?

“oxLDL increased O2– and H2O2 in these cells and induced a dose- and time-dependent reduction in the p-Akt/Akt ratio and increase in EPC apoptosis. These effects were significantly reduced by the antioxidants superoxide dismutase, L-NAME, epicatechin and FeTPPs. oxLDL also induced nitrosylation of the p85 subunit of PI3K…an effect significantly reduced by all the antioxidant agents tested.”

In other words, the ‘bad news’ is that oxidized LDL is ‘death’ to blood vessel cells; the ‘good news’ is that the antioxidants that were examined can protect against this effect. Thus the authors conclude:

“The present findings indicate that oxLDL disrupts the PI3K/Akt signaling pathway at the level of p85 in EPCs. This dysfunction can be reversed by ex vivo antioxidant therapy.”

The serum lipid peroxides (blood) test is our objective indicator for the amount of LDL oxidation.

A new and convenient biomarker for early insulin resistance

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PLoS OneElevated levels of insulin due to insulin resistance can do so much damage throughout the body long before the onset of type 2 diabetes that better tools for making the diagnosis early enough for lifestyle changes to have their maximum benefit are always welcome. This research article just published in PLoS One (Public Library of Science) validates the use of an ‘old friend’, α-hydroxybutyrate (α–HB, α = alpha), as a valuable warning sign in the non-diabetic population. The authors first note that…

“Current diagnostic tests, such as glycemic indicators, have limitations in the early detection of insulin resistant individuals. We searched for novel biomarkers identifying these at-risk subjects.”

The authors use of ‘random forest statistical analysis’ of 399 nondiabetic subjects (representing a broad spectrum of insulin sensitivity and glucose tolerance) selected α-hydroxybutyrate (α–HB) as the most accurate biochemical for detecting insulin resistance.

“α–HB also separated subjects with normal glucose tolerance from those with impaired fasting glycemia or impaired glucose tolerance independently of, and in an additive fashion to, insulin resistance. These associations were also independent of sex, age and BMI.”

Thus the authors conclude:

“α–hydroxybutyrate is an early marker for both insulin resistance and impaired glucose regulation.“

I have been testing α–HB for years as part of an organic acids panel because it is also an indicator of toxin-stimulated upregulation of detoxification pathways and glutathione demand. So it makes sense that the authors would also add:

“The underlying biochemical mechanisms may involve increased lipid oxidation and oxidative stress.”

I’m looking at an organic acids report from the file of a patient with other signs of insulin resistance plus a recurrence of breast cancer and, sure enough, α–hydroxybutyrate is abnormally elevated.