F2-Isoprostanes: A Major Aging Marker of Lipid Peroxidation and Risk Marker for Developing Coronary Heart Disease


Arachidonic acid

Arachidonic acid (AA) is a polyunsaturated omega-6 fatty acid (20:4(ω-6)) and is converted from linoleic acid, which is an essential fatty acid, known as omega-6 fatty acid.

In the body, arachidonic acid is present in the phospholipids of cell membranes and mostly abundant in the:

  • brain
  • muscles (accounting for roughly 10-20% of the phospholipid fatty acid content on average)
  • liver

Only animals and not plants can convert linoleic acid to arachidonic acid.  Arachidonic acid can also be obtained endogenously from the diet by consuming primarily animal foods, such as:

  • meat
  • poultry
  • eggs

Physiologically, the body requires a certain level of AA.  However, when that level is outside the accepted reference range, this can progress into a pro-inflammatory environment.  AA is actually considered to produce various pro-inflammatory eicosanoids. 

Image result for Arachidonic acid

Figure 1.  Arachidonic Acid cascade  (Source)

One measure of cellular inflammation is the AA:EPA Ratio.  The AA: EPA ratio provides a more specific indicator of the balance between omega-6 and omega-3 fatty acids in circulation. When this ratio is higher, there is preferred incorporation of AA into cell membranes over EPA, leading to a pro-inflammatory environment.

While both of these fatty acids are essential to human health, the optimal ratio of AA:EPA is around 1.7.  1 


Isoprostanes are prostaglandin-like compounds formed in the body from the free radical-catalyzed peroxidation of arachidonic acid.  Isoprostanes acts as inflammatory mediators and possess potent biological activity.  They are accurate markers of lipid peroxidation of oxidative stress.  2

Image result for lipid peroxidation

Figure 2.  Harmful Effects of Lipid Peroxidation  (Source)

Lipid peroxidation occurs in the cell membrane when free radicals oxidize or degrades the lipids contain the the cell membranes.  This ultimately results in cell damage.  Polyunsaturated fatty acids (mostly AA) are particularly vulnerable to lipid peroxidation due to the numerous double bonds in their structure.


F2-Isoprostanes are produced by the reaction of free radicals with arachidonic acid.

Image result for F2-Isoprostanes

Figure 3.  Metabolism of F2-Isoprostanes  (Source)

The damage done by F2-Isoprostanes can be widespread, since they can generally cause:

  • blood vessels to constrict
  • blood pressure to raise
  • promotion of blood clots
  • promotion of the clumping of platelets

Numerous studies carried out over the past decade have shown that these compounds are extremely accurate measures of lipid peroxidation and have illuminated the role of oxidant injury in a number of human diseases including atherosclerosis, Alzheimer’s disease and pulmonary disorders.  3

Measuring and Testing for F2-isoprostanes

The F2-isoprostanes test is considered the gold standard for oxidative stress and is measured in a urine specimen. 

Elevated F2-isoprostanes levels are at a more than 30-fold risk for developing coronary heart disease compared with those with normally low levels.  4

According to the Cleveland HeartLab, Inc., your F2-isoprostanes risk is low when your level is less than 0.86 ng/mg; at or above that level places you at high risk.  5


Cleveland HeartLab, Inc.

Reference Range for F2-isoprostanes

Age                                                                ng/mg creatinine

All Ages                                                                  <0.86



Informational References:

Cleveland HeartLab, Inc. offers the F2-isoprostanes Test through the Know Your Risk Program®

Cleveland HeartLab, Inc. F2-isoprostanes Handout

Video:  Marc Penn – Trials and Tribulations of Assessing CVD Risk in 2013 (Cleveland HeartLab)