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Life Extension Magazine

LE Magazine November 2005
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The Perricone Weight Loss Program

By Nicholas V. Perricone, MD

Dangers of Inflammation

Acute inflammation is a protective response of tissue to irritation, injury, or infection and is characterized by pain, redness, swelling, and sometimes loss of function. It is, under normal circumstances, beneficial, and helps the body repair the effects of trauma or infection. However, prolonged, excess, or chronic inflammation becomes harmful.

When low-grade invisible inflammation occurs in the very cells that comprise our organ systems, a concept I introduced in my first book, The Wrinkle Cure (2000), we are placed at great risk for a host of degenerative, age-related diseases. This is because cells that are attacked by self-generated inflammation will not function properly (meaning that we did something to precipitate a pro-inflammatory response in our cells, thus causing malfunction and sometimes complete breakdown).

In other words, cells respond to the way we treat them. If we keep them healthy and free of injury, if we give them the proper nourishment, they keep us alive and running at top form. If we don’t, if we expose them to too much sun, to environmental toxins, to extended periods of stress, or to high-glycemic sugars and starches, the cells will react by producing inflammatory chemicals as a deviation of the normal defense mechanism. And if we mistreat our cells in this way on a regular basis, we can end up with organ system failure and diseases like the ones listed, including metabolic syndrome, which can lead to diabetes and obesity.

This hidden inflammation is a novel and previously unrecognized “missing link” in our obesity epidemic.

This past decade has seen a complete turnaround in the way scientists regard white adipose tissue—better known as body fat. They no longer look upon it as an inert deposit of fat cells, stored as the result of overeating. They now realize that areas of fat storage are actually an active endocrine organ. Fat produces hormones, as do our pancreas, thyroid, parathyroid, adrenals, pineal, pituitary, and testes/ovaries, the organs that comprise the endocrine system. We are beginning to define body fat as a group of cells communicating with other organ systems such as the brain, the liver, the bone marrow, skeletal muscle, the adrenal cortex, the sympathetic nervous system, and the complete immune system. And the message they are communicating is not good.

This is extremely important because the body fat itself controls how much body fat is going to be stored. It also affects our appetite, our energy expenditure, and our immune system. Body fat accomplishes this by secreting hormones known as adipokines. Adipokines are proteins that act as messengers throughout the body (more examples of the communications network). Like certain types of cytokines, those chemical messengers that have pro-inflammatory activity, adipokines can contribute to systemic, low-grade, chronic inflammation.

This becomes even more frightening when we begin to understand that the greater amount of fat we have stored, the greater its negative influence on the entire body, an extremely destructive, inflammatory influence.

In fact, it would not be too great a stretch to compare excess body fat storage to a tumor, for several valid reasons. A large store of body fat can be so overwhelming to the system that the fat cells have to secrete hormone-like substances to increase blood vessel growth necessary to feed the accumulation of fat. In addition, like a tumor, blood vessel growth cannot keep up with the rapidly growing mass of fat cells, which then begin to become oxygen-starved. These oxygen-starved cells start releasing inflammatory chemicals to further trigger blood vessel growth. These same events are seen in tumor growth, as well.

Most overweight people, especially the obese, have chronic high levels of insulin that will begin to drop as soon as they start dieting. This is a two-edged sword, as low insulin levels decrease inflammation, which allows us to utilize body fat for energy. However, insulin is required to bring protein into the cells to maintain muscle mass. The overweight or obese person has cells that are insensitive to insulin due to their chronic high levels. That is, their body is so used to the overly high levels, it cannot recognize these new lower levels, thus it is unable to trigger the amino acid uptake needed to maintain muscle mass (insulin is needed to take up both sugar and amino acids into the muscle).

This is why it is critical to take a powerful anti-inflammatory approach to dieting. Remember, it is the inflammatory chemicals, such as NfkB, that block the effects of insulin—whether it is to metabolize blood sugar or to nourish muscles with amino acids. Over-exercising can further put us into a catabolic state (in which complex molecules are broken down into simpler ones) because of the higher requirement of nutrients needed for active muscles.

Inflammation, Body Fat, and Heart Disease

Scientists and physicians now recognize that heart disease is mediated by inflammatory chemicals. In fact, forward-thinking cardiologists are now measuring C-reactive protein, a marker of inflammation, to identify patients at risk for heart disease. This is proving to be significantly more accurate than looking at cholesterol. In fact, many cardiologists now report that elevated C-reactive protein is four times more accurate in predicting heart disease than elevated cholesterol.

C-reactive protein is a special type of protein produced in high amounts by the liver during episodes of acute inflammation. High circulating levels of C-reactive protein also indicate stomach inflammation. Researchers at UC Davis recently found that endothelial cells (the delicate lining of the circulatory system) also produce C-reactive protein, a key finding that helps to explain how plaque formation is initiated. This is particularly important because endothelial cells are supposed to protect the arteries from the effects of C-reactive protein. Researchers also found that C-reactive protein can cause these endothelial cells in our arteries to produce a substance called plasminogen activator inhibitor, which leads to blood clot formation.

C-reactive protein can also lead to activation of white blood cells in the lining of the arteries to promote plaque formation. These findings begin to explain why those individuals with excess body fat are at a higher risk for cardiovascular disease. Scientists have discovered that excess weight leads to low-grade chronic inflammation; low-grade, chronic inflammation leads to mildly elevated C-reactive protein, which can lead to heart disease. As the pieces of the puzzle began to come together, I began to understand why people were losing weight on my anti-inflammatory diet. The foods and supplements that I had been recommending to reduce wrinkles and slow down the aging process were also inhibiting the inflammation that causes insulin resistance and body fat storage.

DANGERS OF ELEVATED NfkB

What happens (besides elevating our risk for disease) when people who are carrying excess fat have elevated levels of NfkB?

• It interferes with the body’s ability to use insulin,
• increasing our blood sugar levels,
• which then further increases inflammation,
• and makes us store body fat.

As mentioned, I advocated eating ample quantities of cold-water fish like wild Alaskan salmon, sardines, anchovies, mackerel, herring, shad, and trout—ideally, one fish meal per day. I also strongly recommended the use of nutritional supplements like omega-3 fish oil, alpha lipoic acid, carnitine, CLA (conjugated linoleic acid), glutamine, coenzyme Q10, astaxanthin, and dimethylaminoethanol (DMAE).

Why are these foods and supplements so effective? Because they all have high anti-inflammatory properties. Brightly colored fruits and vegetables signal the presence of antioxidants, nature’s natural anti-inflammatories. Wild Alaskan salmon also contains a powerful antioxidant, anti-inflammatory (responsible for its deep pink/red coloring) known as astaxanthin, reported to be more than 100 times stronger than vitamins C and E combined. Further, I realized that the single most powerful causative agent for reducing inflammation was the high levels of essential fats that I was recommending. These fats, particularly the omega-3 essential fatty acids found in high-fat fish and fish oil, act as powerful, natural anti-inflammatories.

Recognizing that a great many Americans were overweight, and their diets were practically devoid of the omega-3s, I asked myself the following questions: Could it be that low levels of the essential fatty acids exacerbate inflammation and promote weight gain? And could it then be that high levels of essential fatty acids also reduce the inflammation that is found in people with excess body fat, thereby accelerating that loss?

Perhaps we can find the answer in the huge increase of overweight people that has its roots in the no-fat and low-fat craze of the 1980s and continues to escalate to this day. Women in particular have suffered from the ridiculous and dangerous notion that all fat is bad and must be avoided at all costs. Not only did they not lose weight, this dangerous fad accelerated the development of wrinkles and contributed to an epidemic of mental depression and obesity.

The reason for this is twofold. First, the onset of the low-fat diet deprived brain cells of the critically essential healthy fat needed for normal brain function. When I say “normal” brain function, I refer to the production of those important chemical messengers known as “neurotransmitters” that allow brain cells to communicate with one another. We all know from television and magazines that low levels of serotonin, the classic “feel good” neurotransmitter, can lead to chronic depression. By depriving the brain of the healthy fats it needs to produce serotonin and other neurotransmitters, we are effectively opening the door to depression and a host of other mental, behavioral, neurological, and psychological maladies.

Second, in addition to the damage done by the deprivation of healthy fats, the 1980s saw the rise in the ingestion of massive quantities of fat-free, high-glycemic carbohydrates, such as the ubiquitous rice or corn cake, baked potato chips, nonfat cookies, and so on, which has played a significant role in the epidemic of both obesity and type II diabetes.

When we eat these high-glycemic carbohydrates, we deplete our precious reserves of serotonin. For example, a breakfast consisting of a low-fat muffin or bagel with fat-free cream cheese and jam, and a glass of fruit juice, will cause a rapid rise in blood sugar. This results in a release of serotonin in the brain, giving us a warm, fuzzy feeling as the carbohydrates are rapidly converted to glucose (sugar) by our digestive system. High levels of sugar are now circulating in our bloodstream, which signals the pancreas to secrete insulin to help bring down these high levels of sugar. The problem begins when the insulin pushes the blood sugar levels down to levels too low. The result is a rapid decline in serotonin levels, a quick drop in energy—and an almost irresistible craving for more sugar and carbs.

In other words, we need another “fix” in order to get back the warm, fuzzy feeling. In fact, many women “self-medicate” with high-glycemic carbs in their rational desire to simply feel good. I say “women” here because women generally tend to have lower levels of serotonin than men. And these levels drop even lower during parts of the menstrual cycle and when they are postmenopausal. To compensate for this, women resort to consuming larger amounts of high-glycemic carbohydrates than their male counterparts. Since many women place themselves on calorie-restricted diets, they then tend to forgo healthy proteins and healthy fats to make up for the calories contained in the carbohydrates.

This often results in women looking older than men of their same age group, because healthy fats and protein are necessary for cellular repair, while high-carb diets accelerate the aging process. The fluctuating blood sugar and insulin levels place them in a constant battle with excess weight gain, while the depletion of their serotonin leaves women at greater risk for depression.

This sorry state of affairs is contributing to the breakdown of the mental and physical health of men, women, and children at an escalating rate. We are overweight, we are depressed, we are fatigued, and we are stressed. And more and more of us, children and adults alike, are turning to chemical and pharmacological solutions to the problem. However, these “solutions” treat the symptom while ignoring the underlying problem. There is a better way.

I soon learned that when you consume food, its energy (measured as calories) can take one of two paths in the body:

  • Food calories can be burned in the mitochondria for production of ATP (adenosine triphosphate), a high-energy phosphate molecule used to store and release energy for work within the body. This entire process is known as “oxidative phosphorylation.”
  • More often as we get older, the food can go on to be stored as body fat (triglycerides in adipose tissue) or stored as glycogen in the liver and muscles (glycogen is the form in which foods are stored in the body as energy). If we can “uncouple” the oxidation from the phosphorylation, food calories can be burned off by thermogenesis. Thermogenesis bypasses the ATP-mediated energy. If the majority of food we ate was transformed into body heat, we would stay slim and trim.

This research led me to create the anti-inflammatory diet, where I discovered that the omega-3 essential fatty acids (EFAs) were powerful anti-inflammatories.

One important role of EFAs turned out to be their effect on insulin levels. High levels of insulin are pro-inflammatory; this is one of the reasons people gain excess weight and cannot seem to lose it when they diet. Chronically high levels create an “insensitivity” to the insulin. Excess insulin continues to be released into the bloodstream, resulting in the storage of fat.

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