The Mediterranean Zone (14 page)

The immune cells that generate these free radicals come from otherwise benign white cells circulating in your bloodstream. Once the innate immune system senses the existence of microbial fragments, a complex process is started that transforms the white blood cells happily circulating in your bloodstream into the cellular dogs of war (neutrophils and macrophages) to do battle against microbes. Just like radiation coming from X-rays (or an atomic bomb blast), these free radicals generated by neutrophils and macrophages are killers. Eventually, these biological rogue warriors must be called off during the resolution phase of the inflammatory response, which is described in greater detail in the Appendices.

The resolution phase of inflammation shuts down the inflammatory attack by the synthesis of powerful hormones called resolvins, derived from omega-3 fatty acids (EPA and DHA). Without adequate levels of omega-3 fatty acids in the diet, the resolution phase of inflammation will be compromised. These resolvins are critical for causing the destruction of the newly generated neutrophils and macrophages and returning the body back to equilibrium. If the initial inflammatory signal is too strong, or if the resolution response for turning off the initial inflammatory response is too weak, then these immune cells continue to hang around, spewing out a continual stream of free radicals.

Another source of free radicals is the constant need to convert dietary calories into chemical energy (usually the molecule adenosine triphosphate, or ATP). The amount of calories you consume doesn’t count as much as the efficiency of their conversion into ATP. Without adequate levels of ATP, your cells can’t function efficiently to maintain your metabolism
and cellular renewal, nor can you maintain enough energy for the physical demands on your body, such as walking or running. The conversion of dietary calories into ATP takes place in the mitochrondria found in every cell in the body. The process of making ATP requires the generation of a lot of free radicals, and invariably some of these free radicals escape. Obviously, the fewer the calories you eat, the fewer free radicals you make. This is one of the reasons calorie restriction (without malnutrition) slows down the rate of aging. Restrict calories and add more polyphenols to your diet, and you can live even longer.

The strength of an anti-oxidant molecule can be measured by its ability to neutralize free radicals. This can be quantified in a test tube to provide a quantitative ranking system known as the oxygen radical absorption capacity (ORAC), which estimates the potential of a given amount of a food product to act as an anti-oxidant. It has been shown that the ORAC value of a food ingredient is correlated with the levels of polyphenols in the same ingredient. Some polyphenols are best at neutralizing free radicals in the water-soluble environment (such as in your blood) whereas others work best in the lipid environment (as in lipoprotein particles or in cell membranes). Therefore what you need is a total ORAC value that represents the combination of both types of anti-oxidant activities. The higher the total ORAC level of a food ingredient, the better its potential ability to act as an anti-oxidant.

Listed below are some of the total ORAC values of common foods. A more complete list can be found in Appendix G.

Looking at the chart above, it is not clear why eating broccoli is a better dietary choice than pumpernickel bread. It is only apparent when you take into account the amount of carbohydrates you are simultaneously ingesting to obtain those anti-oxidative polyphenols. So let’s redo the same table and see what food item provides the greatest amount of anti-oxidants with the least amount of absorbable carbohydrates (defined as total carbohydrates minus fiber).

As you can see above, the levels of polyphenols per gram of carbohydrate is seven times greater in broccoli than pumpernickel bread. This means you would be consuming seven times more carbohydrates by eating pumpernickel bread instead of the broccoli to get the same levels of anti-oxidants. To make this comparison even more compelling, the carbohydrates in the pumpernickel bread (as with all whole grains) are composed of virtually 100 percent glucose, whereas the carbohydrates in fruits and vegetables have lower levels of glucose and higher levels of fructose. The more glucose you consume, the more insulin you secrete. And if you are consuming a lot of omega-6 fatty acids at the same time, you will be generating more cellular inflammation. Frankly, it just isn’t worth the hormonal hassle to eat whole grain breads and cereals to get the necessary levels of polyphenols you need to reduce oxidative stress.

I can do the same type of calculations for herbs and spices using dried rosemary as an example.

Obviously, no one is going to eat 100 grams (which is 3.5 ounces or nearly 10 tablespoons of dried rosemary), but you can quickly see that rosemary (such as most spices) is a tremendous source of anti-oxidants with very little accompanying carbohydrate.

Here is another problem: It does not matter how many polyphenols you consume, but how many of those get into the bloodstream to exert their anti-oxidant actions. Only 2 to 20 percent of consumed polyphenols actually enters into blood. Once a polyphenol enters the blood, it is rapidly metabolized so that it can be excreted. A polyphenol is at its peak level usually within two hours of consumption, then is rapidly metabolized and is completely eliminated from the body, usually through the urine, within twelve hours. This means that virtually all the polyphenols consumed in a meal are out of your body within twelve hours. To maintain a constant
level of these powerful anti-oxidants in the blood you either have to have a lot of colorful carbohydrates at every meal or take a very large amount of purified polyphenols several times a day.

So how do you know if the polyphenols you are consuming are actually doing you much good? You really have to look at indirect markers of reducing oxidative stress. One of these markers is the level of oxidized LDL.

For more than forty years, the medical community has been misled in thinking the level of total LDL cholesterol is a driving force for the development of heart disease. Actually, a major culprit in heart disease is not plain old normal LDL particles, but oxidized LDL particles. Oxidized LDL particles are able to sneak into the cell through a backdoor pathway, whereas normal LDL particles cannot. Thus much of the accumulated cholesterol in an atherosclerotic plaque is composed of oxidized LDL particles. Until recently, measuring oxidized LDL directly was very difficult and as a result, calculating total LDL cholesterol has been unknowingly used as a surrogate marker for oxidized LDL without anyone realizing it. The real relationship between heart disease and cholesterol was really one based on the levels of oxidized LDL particles.

Statins became the most profitable drugs in history because while they were lowering normal LDL cholesterol they were also lowering the levels of oxidized LDL. But with statins it was a case of throwing the baby out with the bathwater since you need normal, non-oxidized LDL to deliver adequate levels of cholesterol to the brain to maintain cognitive function. This is why one of the major side effects of statins is memory loss. Polyphenols, on the other hand, can directly reduce the levels of oxidized LDL without reducing LDL cholesterol. That’s one of the reasons adherence to the traditional Mediterranean diet simultaneously reduces heart disease and improves cognitive function in the brain.

The dual power of polyphenols for both heart and brain health was demonstrated using high-dose polyphenols derived from blueberries in two separate clinical studies in 2010. One study at the University of Oklahoma demonstrated a statistically significant 30 percent reduction in levels of oxidized LDL. The other study at the University of Cincinnati demonstrated significant improvement in cognition in older adults with impaired memory. It should be noted that delphinidins are one of the major classes of polyphenols in blueberries. If blueberries are good, then purified polyphenol extracts from the maqui berry I described earlier should be better
as they are fourteen times more concentrated in delphinidins than blueberries. It appears that if you consume enough polyphenols (and delphinidins look like a really good choice), then your likelihood of heart disease and Alzheimer’s should be reduced.

So how many ORAC units do you need to consume on a daily basis to get a sufficient amount of polyphenols? If you consume the recommended five to nine servings of fruits and vegetables per day, which virtually no one in America does, you would probably get about 3,000 to 5,000 ORAC units per day. A study at Tufts Medical School in 1996 indicated if you increased your intake to ten servings of common fruits and vegetables per day, you would consume about 6,000 ORAC units per day. Even though you are doubling the dietary intake of polyphenols, the anti-oxidant levels in the blood increase by only about 10 percent because most polyphenols have a very low absorption rate by the body. Although this may seem like a case of diminishing returns, if you consume enough polyphenols on a daily basis, the payoff in reducing the oxidative stress on the body is remarkable. What I generally recommend is the daily consumption of about 10,000 ORAC units to reduce oxidative stress. To reach that, you will probably need to supplement your consumption of colorful carbohydrates with perhaps a glass of red wine, adding a couple of tablespoons of authentic extra-virgin olive oil, or taking highly purified polyphenol extracts in a pill or liquid form.

However, what truly makes polyphenols unique in addition to their ability to neutralize free radicals is their ability to increase the production of additional powerful anti-oxidant proteins by binding them to a specialized gene transcription factor. Every cell contains unique proteins called gene transcription factors that let the cell fine-tune the expression of its gene responses to its immediate environment by turning unique sets of genes on or off. The one such gene transcription factor activated by polyphenols is known as Nrf2. Once it is activated, it can accelerate the synthesis of a wide array of additional powerful anti-oxidative proteins. These proteins not only effectively neutralize free radicals but also regenerate other anti-oxidant molecules. Polyphenols should really be viewed as super anti-oxidants because they’re able to quench free radicals very effectively on their own, but they also have the ability to enlist the synthesis of new anti-oxidant enzymes so that you can continue your lifelong struggle against oxidative stress.

Can you take too many anti-oxidants? Of course you can, especially if they are the kind of anti-oxidants that easily enter into the blood, such as vitamin E, beta-carotene, and vitamin C. This is especially true if you are taking chemotherapeutic drugs that rely on increased free radical generation caused by the cancer drug to kill the cancer cells by causing fragmentation of its DNA. Likewise, too many anti-oxidants in the blood can blunt the ability of the immune system to destroy invading microbes as well as potentially creating pro-oxidant effects. However, most people have enough trouble eating my recommended daily servings of fruits and vegetables to get the necessary polyphenols they need. That’s why your grandmother told your parents that they couldn’t leave the dinner table until they had finished all their vegetables. Who knew that Grandma was the cutting edge of twenty-first-century biotechnology to reduce oxidative stress?

A
s important as polyphenols are in reducing excess free radicals and oxidative stress, their most important property may be their ability to slow the rate of aging.

Who doesn’t want to live longer? One of the first indications that it was possible to extend your life through diet came from the writings of Luigi Cornaro, a Venetian nobleman, who lived in the fifteenth century. Finding himself near death at age 35 because of his rich dietary lifestyle, he went on a strict calorie-restricted diet consisting of an egg yolk, some vegetable soup, small amounts of locally grown fruits and vegetables, and a very small amount of coarse, unrefined bread, as well as three glasses of red wine per day. He wrote his first anti-aging book,
The Sure and Certain Method of Attaining a Long and Healthful Life,
at age 83 and his third anti-aging book at age 95. He died at age 99. At the end of his life he was still mentally sharp and physically active.

Nearly four hundred years later in 1935 Clive McCay demonstrated that calorie restriction could dramatically prolong the lifespan of rats. Since then the benefits of calorie restriction have been reproduced in a wide number of other animal species. Luigi Cornaro’s highly restrictive caloric diet can be estimated to have been between 800 and 1,000 calories per day,
hardly enough calories to generate the chemical energy a human needs to live. But obviously Luigi did a pretty good job for ninety-nine years. Is it possible that the polyphenols in the red wine also helped? The answer may be yes.