A report today (May 18, 2006) really put a smile on my face, I must admit, because it is so consistent with my interpretation of the scientific evidence, but it also demonstrates why you should be careful about taking large amounts of antioxidant supplements. So let's get to the report, which opens with:

"Doctors have long been encouraging Americans to add more fruits and vegetables to their daily diets. Now, UC Davis researchers have discovered one way in which flavonoid-rich apples inhibit the kinds of cellular activity that leads to the development of chronic diseases, including heart disease and age-related cancers."

Source: http://www.sciencedaily.com/releases/2006/05/060517185449.htm

As I point out, much of this "cellular activity" involves AA metabolites, which one can easily avoid with the right diet. But then comes the really interesting part:

"In the current study, Gershwin and his colleagues exposed human endothelial cells to an extract of an apple mash made from different apple varieties. The researchers then challenged these cells by exposing them to tumor necrosis factor (TNF), a compound that usually triggers cell death and promotes inflammation via a mechanism called the 'nuclear factor (NF) kappa B pathway.' This pathway involves chemical signaling between cells. The apple extract was able to protect the cells from the normal lethal effects of TNF."

If you've read the other essays, you know that the more unsaturated the fatty acids in your cells, the more TNF gets generated during stress to cells. But the nuclear factor kappa B pathway is important here as well. I'll let some scientists who seem to really understand the material explain it:

"N-6 polyunsaturated fatty acids (N-6 PUFAs), major constituents of corn oil and natural ligands for peroxisome proliferator-activated receptors, increase the rate of growth of established tumors. It has been proposed that chemical peroxisome proliferators increase hepatocyte proliferation by mechanisms involving activation of nuclear factor-B (NF-B) and production of low levels of tumor necrosis factor (TNF) by Kupffer cells; however, how N-6 PUFAs are involved in increased cell proliferation in liver is not well understood. Here, the hypothesis that N-6 PUFAs increase production of mitogens by activation of Kupffer cell NF-B was tested. A single dose of corn oil (2 ml/kg, i.g.), but not olive oil or medium-chain triglycerides (saturated fat), caused an ~3-fold increase in hepatocyte proliferation. Similarly, when activity of NF-B in whole rat liver or isolated hepatocytes and Kupffer cells was measured at various time intervals for up to 36 h, only corn oil activated NF-B. Corn oil increased NF-B activity ~3-fold 1�? h after treatment exclusively in the Kupffer cell fraction. In contrast, increases were small and only occurred after ~8 h in hepatocytes. The activation of NF-B at 2 h and increases in cell proliferation at 24 h due to corn oil were prevented almost completely when rats were pretreated for 4 days with either dietary glycine (5% w/w), an agent that inactivates Kupffer cells, or the NADPH oxidase inhibitor, diphenyleneiodonium (s.c., 1 mg/kg/day). Furthermore, arachidonic acid (100 µM) activated superoxide production ~4-fold when added to isolated Kupffer cells in vitro. This phenomenon was not observed with oleic or linoleic acids. Interestingly, a single dose of corn oil increased TNF mRNA nearly 2-fold 8 h after treatment. It is concluded that corn oil rapidly activates NF-B in Kupffer cells via oxidant-dependent mechanisms. This triggers production of low levels of TNF which is mitogenic in liver and promotes growth of hepatocytes...

In conclusion, the data presented here support the hypothesis that corn oil activates NF-B in Kupffer cells via oxidant-dependent mechanisms. This is probably a key early event resulting in subsequent increases in TNF leading to increased cell proliferation in the liver"

Source: Carcinogenesis, Vol. 20, No. 11, 2095-2100, November 1999

So here again the connection between diet and the "disease" common in the West today is clear. As I've said in other essays, my main point is that there is enough scientific evidence to make clear suggestions about diet, and that most of what you hear in the media is the opposite of what you should be doing, especially concerning which fatty acids are best and which are the worst.

Now for the point about antioxidants: if you follow my diet, for example, you may do harm if you use antioxidant supplements in large amounts (and that might happen with any diet). Why? Because molecules like TNF are useful under certain circumstances, and if you inhibit them in a strong way you might cause "disease." The reason why antioxdant "studies" look "good" has to do with the fact that almost everyone is eating a diet that produces a lot of free radical damage. In theory, one might be able to "balance" these two sides of the coin (called the redox balance), but much more experimentation would have to be done to see what the long term effects are of various combinations. Until then, I will stay with my diet and no antioxidant supplements (though as I get older I might take small amounts of CoQ10).