Sunday, November 1, 2009

Inflammation and Oxidation

Inflammation and oxidation contribute to many, if not most, diseases.

Based on this observation one would suspect that anti-inflammatories and antioxidants should prevent many diseases. Indeed, there is excellent data that anti-inflammatories can help prevent many diseases. However, support for antioxidants is more limited.

First, antioxidants.

There are a number of antioxidants that one must consume (e.g., vitamin E, vitamin C, zinc, and selenium). There is a lot of mileage in making sure that one is not deficient in any of these antioxidants. However, there is decent evidence that, in general, after sufficiency is attained, more is not better.

The body also has a number of in-house antioxidants, known as endogenous antioxidants (e.g., superoxide dismutase, glutathione peroxidase, alpha lipoic acid, catalase and coenzyme Q10). Many external, or exogenous, antioxidants (like the vitamins and minerals mentioned above) are necessary to maintain proper levels of these all-important endogenous antioxidants. Moreover, many exogenous antioxidants also happen to have other biological effects aside from reducing oxidation (e.g., some have anti-inflammatory effects and some are polyphenols with diverse effects)

And, that might very well be all there is to exogenous antioxidants -- they're important, but perhaps not because of their (direct) capacity to reduce oxidation...

And now, inflammation.

Inflammation generally starts with injury (e.g., acid or bile injury in the case of esophagitis). The body responds to an injury by sending lots of blood to the area to address the underlying problem. The body's response is modulated by a cascade of signaling molecules designed to cause the inflammatory reaction.

On a molecular level, the signaling cascade starts with omega 3 and omega 6 fatty-acids. These fatty-acids, made from dietary polyunsaturated fat, are turned into signaling molecules called eicosanoids. Two families of enzymes catalyze fatty acid oxygenation to produce the eicosanoids: (1) cyclooxygenase, or COX, which generates the prostanoids (Cox-2 generates PGE2) and (2) lipoxygensase, or LOX ( 5-LOX generates the leukotrienes).

It turns out (and this is a bit of a simplification) that there are two broad types of prostanoids and leukotrienes: (1) inflammatory prostanoids and leukotrienes and (2) anti-inflammatory prostanoids and leukotrienes. Significantly, omega 6 fatty acids are the precursors to the inflammatory prostanoids and leukotrines while omega 3 fatty acids are the precursors to the anti-inflammatory prostanoids and leukotrines.

Almost all modern people eat way more omega 6 than omega 3 fatty acid (some eating 50 times more). Unfortunately for us, most people for the last 2 million years ate a fairly even ratio. Sounds like trouble...

With such an over-abundance of omega 6 in our tissue, there generally aren't enough omega 3 precursors present to be made into anti-inflammatory signaling molecules. Chronic inflammation, inflammation that outlives its biological purpose, seems to be the result.

Tissue highly unsaturated fat (omega 3 and omega 6) has a two-year half-life on average. That means that it takes two years for your body to replace half this fat in your body. In addition, omega 6 oil is ubiquitous in our food supply (vegetable oils, corn/soy fed animal, nuts & seeds). Thus, replacing all that tissue omega 6 with tissue omega 3s takes a long time and is hard to do. That said, I am currently in the process of doing it because it is the actual cure rather than the band aid.

In the meantime, NSAIDs can help to stop chronic inflammation by inhibiting the Cox-2 enzyme and/or by inhibiting the 5-Lox enzyme (by the way, it might be ideal to inhibit both Cox-2 and 5-Lox at the same time). Turmeric, ginger, green tea, french pine bark, and numerous other natural compounds inhibit both enzymes. In addition, aspirin is a potent inhibitor Cox enzymes and boswellia is a potent inhibitor of 5-Lox.

In the context of the chemoprevention of esophageal cancer in people with Barrett's esophagus, there is very good epidemiological data for aspirin. Indeed, aspirin is currently the subject of a placebo-controlled trial in England, which should produce some preliminary data in 2011. However, aspirin's effect on cancer progression, if any, might be due to mechanisms other than Cox-2 inhibition (as suggested by a trial, albeit a small & short one, in which selective a Cox-2 inhibitor didn't perform so well). For instance, aspirin also promotes cellular adhesion. (I believe that the authors of the U.K. trial also share my suspicions about aspirin as the dose they are using, 300mg, is well in excess of the dose required to effectively inhibit Cox-2, suggesting they are interested in exploring some of the other benefits of aspirin.)

I know this sounds like a broken record, but vitamin D also promotes cellular adhesion, probably better than does aspirin.


  1. Great post. Will add some ayurvedic boswellia to my personal regimen.

  2. I see that you are trying to avoid developing cancer with a low-carbohydrate diet, with most of your fats coming from dairy, omega-3 eggs, and grass fed beef. I must say, I am shocked that you have come up with this regimen and have to wonder where exactly you came up with this. Vast medical studies have shown a direct link between cancer and a diet high in animal protein. In a study done with rats injected with the carcinogen aflatoxin, with half of the rats being fed a 20% animal protein diet, and half of the rats being fed a 5% animal protein diet, all of the rats on the higher animal protein diet developed cancer or its precursor lesions within 2 years, while none of the rats fed the low animal protein diet did. The protein used was casein, the same protein you are drinking in cow's milk. This experiment was then duplicated by Dr. T. Colin Campbell, with an NIH funded grant. The results were exactly the same.

    Furthermore, even when the experiment was tweaked, and more aflatoxin was given to the low protein rats, cancer developed at a drastically retarded rate. On the flip side, when less aflatoxin was given to the high protein rats, cancer still developed at an extremely accelerated rate.

    When the protein was switched to a soy-based protein, however, both sets of rats showed a very diminished cancer rate, even with fantastic doses of aflatoxin.

    There are many studies showing the adverse effects of animal protein in the development of cancer, heart disease, osteoporosis, etc. but they are too numerous to name. I recommend staying away from gimmick diets, junk-science diet books and amateur diagnostics and picking up a copy of "The China Study", which takes an actual scientific approach to diet, and cites thousands of legitimate, peer-reviewed scientific diet studies regarding the relationship between diet and disease. The diet you are on currently is simply not congruent with your goals and will do you more harm than good in the long run. If you would like to contact me, you can e-mail me at

  3. Acorn,
    Thanks for your comment. First, the China Study is simply a collection of associative studies incorporating the same biases. Generally, after years of bad health advice, the health-seeker will adjust their habits while the non-health seekers do not. Associative studies detect the health difference between health-seekers and non-health-seekers. In other words, correlation, not causation.

    You are correct to point out that study re animal protein. There are other studies finding high protein diets ain't so great too. But, I am not advocating a high protein diet. I am advocating a high fat diet.

    Also, I avoid casein as much as possible since it is a troublesome protein. In addition to what you cited, I would point out that casein also (i) stimulates production of IGF1, (ii) negatively modifies function of phenolic compounds, and (iii)disrupts cellular tight junctions. I avoid/limit casein by choosing dairy fats like butter and heavy cream that have little protein. Sometimes I add back some whey protein isolate.

  4. By the way, check out this recent study:

  5. By the way, you should go back and lok at the findings of the actual China study, not the book.

    Sugar, soluble carbohydrates, and fiber all have correlations with cancer mortality about seven times the magnitude of that with animal protein, and total fat and fat as a percentage of calories were both negatively correlated with cancer mortality.

  6. Daniel,
    The study you referred mentions that higher intake of omega-3 fatty acids and high fiber intake results in a decreased risk of esophageal adeoncarcinoma. I wonder if you have ever tried chia seeds. They are high in both omega-3 fatty acids and fiber. Per 28g of chia, there is 8.6g of fat (6.5g polyunsaturated), 10.6g of fiber and 4.4g of protein. They would seem to be perfect for your high-fat diet. If not, I recommend They have the best prices, as well as a host of other products that you may be interested in. Good luck, and good talking to you.

  7. Thanks acorn. I try to achieve balance between omega 3 and omega 6 while also limiting overall polyunsaturated fats. Good luck to you too.