Closely related to maintaining a lean body weight is the practice of caloric restriction, or CR. There is now extensive evidence across a wide range of animal species that restricting calories slows down aging and can extend both life and youthfulness. These experiments have not run long enough to demonstrate actual life extension in humans, but studies of humans practicing caloric restriction show the same reduction in disease and aging markers (changes associated with increasing age) that we see in animal populations. More than 2,000 animal studies show the same dramatic results across many different species.
A highly publicized experiment in 1982 involving rats first introduced the world to CR. The control group was fed a normal diet and lived a normal maximum life span of approximately 1,000 days. Typically, the control rats died from the deterioration of their hearts, kidney disease, or cancer. The diet of the experimental group (the CR rats) contained one-third fewer calories than the control group, but otherwise had adequate nutrients, including vitamins, minerals, protein, and essential fatty acid s. The CR rats lived for about 1,500 days, or 50 percent longer.
Equally significant, the researchers noted a slowing of the aging process. Not only did the CR rats live longer, they largely avoided the feebleness, poor health, sluggishness, and grizzled appearance that accompanied the old age of the normal-eating group, even toward the very end of their extended lives. For example, the coats of the normal-eating rodents, which are smooth and white early in life, typically turn gray and oily by 20 months of age. The CR rodents, in contrast, kept their fur white and shiny for 40 months or more. The low-calorie rats were also significantly more successful at running mazes than normal-eating rats of the same age. Rates of diabetes and cataracts and the strength of the immune system were all dramatically better in the CR rodents.
Long after the normal—eating rats had died, the calorically restricted rats continued to have shiny coats, very low rates of cancer and other diseases, and the higher levels of energy and responsiveness associated with youth. When these CR rats finally died, they often appeared to do so for no obvious reason-probably just old age. According to Dr. Edward Masoro, a physiologist at the University of Texas Health Science Center in San Antonio, “When we look inside them, they’re completely clean.”
Other experiments have exposed both calorically restricted and normally fed rats to high levels of carcinogens. CR rats showed significant resistance to the cancer-causing chemicals, whereas normal-eating rodents easily succumbed. Even strains of rats that are specially bred to be prone to cancer and to autoimmune and other diseases gained significant protection from a low-calorie diet. Dr. Richard Weindruch, a gerontologist at the University of Wisconsin at Madison, comments, “Any kind of screwed-up animal seems to benefit from caloric restriction.
Numerous experiments conducted on a wide range of other animals have shown consistent results. The CR animals live about 30 to 50 percent longer, age more slowly, and are generally much freer of disease, even toward the end of their longer life spans.
How does CR work?
So why does caloric restriction work? Scientists created a genetically modified mouse that lacked a single gene that controls insulin’s ability to enable fat cells to store fat. These FIRKO (Fat-specific Insulin Receptor Knock Out) mice ate substantially more than normal mice—in fact, as much as they wanted, yet they had 50 to 70 percent less body fat. They were also resistant to diabetes, remained healthier longer than the control animals, and lived 18% longer.
Low body fat. Although the diet of the FIRKO mice was just the opposite of caloric restriction, they obtained at least some (although not all) of the benefits of CR anyway. This suggests that at least one mechanism behind CR is simply maintaining a low level of body fat.
Blood glucose level. Both FIRKO mice and low-calorie animals have significantly lower blood glucose levels. That’s because these animals burn glucose for fuel at the same rate as the normal-eating animals; but with less caloric intake, there is less unused glucose left over
Level of free radicals. These highly reactive molecules are by-products of improper metabolism of food. Free radicals cause a gradual deterioration of body tissues, particularly fragile cell membranes. Many researchers attribute some aging processes to the effects of free radicals circulating in the bloodstream.29 The CR animals had substantially lower levels of free radicals (the result of less food metabolism), so they had less free-radical damage to cell membranes. Researchers have also discovered that the levels of a liver enzyme that detoxifies free radicals are about 60 percent higher in low—calorie animals.
DNA repair
Other researchers have discovered that CR animals have more robust DNA-repairing enzymes. Deterioration in the DNA code causes cancer and accelerates other aging processes, so the greater effectiveness of these enzymes would partially account for the slower aging and lower rate of tumors in these animals.
Life calorie limit. It is interesting to note that the total lifetime quantity of food eaten by CR animals and normal-eating animals was roughly the same. The low-calorie animals ate approximately two-thirds as much food per day but lived 50 percent longer, so the total amount of food eaten over their life span was about the same as that of the normal-eating animals. This is consistent with the idea of living cells as heat engines that wear out with the consumption of fuel rather than the passage of time. Hence the wisdom in T. S. Eliot’s quotation: “Our lives are measured, if not in coffee spoons, then in the calories of food that our spoons contain. ”
Each species seems to have a fixed number of calories that it can bum in the course of a lifetime. By eating a little less each day, there will be more days before these calories are used up. Of course, we intend to overcome this and other biological restrictions, but in the meantime we can take advantage of these insights into biology’s limitations.
But there is a limit to the ability of caloric restriction to extend life. Because of the need to obtain sufficient nutrients, we cannot, for example, restrict calories to, say, a third of normal levels and expect to live three times as long. Without adequate vitamins, minerals, protein, and other nutrients, a human or other animal will become ill and
ultimately die if the deficiency is not reversed. It appears that, at least in the case of animals such as rats, the optimal level of calories for longevity is about two-thirds that of what the animals will consume if they are eating freely. Below that, it is difficult or impossible to obtain adequate nutrition.
Applying CR To Humans
There have been a number of human population studies that illustrate the potential of caloric restriction for humans. For example, the people living in the Okinawa region of Japan have 40 times the number of centenarians (people age 100 or older) than the northeastern prefectures, and they have very little serious disease before age 60. Okinawans remain active much longer than their peers in other regions of Japan. The primary difference in their diet appears to be a lower caloric intake.
In applying the animal studies to humans, some researchers have estimated that our maximum life span might be extended from 120 years to 180. Of course, very few of us live to 120 as it is. These estimates refer to a theoretical maximum potential life span Perhaps more significant: this implies that by eating a diet low in calories but otherwise healthy, we are more likely to take full advantage of our current biological longevity.
The benefits of caloric restriction also extend to your remaining life expectancy. If you are 40 and thus have a remaining life expectancy of about 40 years, you will be extending only that remaining period. The earlier you start CR, the greater the benefits. Regardless of when you start, you’ll quickly realize the benefits.
Guidelines For Caloric Restriction
One result of restricting calories is, of course, losing weight. People who follow strict caloric restriction guidelines end up being very thin to the point of looking gaunt, which we don’t recommend. From a recent study, it is clear that at least some of the benefits of CR come from the resultant low level of body fat. Our recommendation, therefore, is to practice a moderate form of CR, not as austere as the 35 percent reduction used in the animal experiments. We suggest the following guidelines:
Eat a minimum of 12 calories per pound of your optimal weight. For example, a man with an optimal weight of 150 pounds should eat a minimum of about 1,800 calories per day; a woman with optimal weight of 125 pounds should eat at least 1,300 calories per day. Depending on your activity level, these figures are 10 percent to 33 percent lower than recommended in the above tables of maintenance calories.
Set your minimum weight at 95 percent of your optimal weight based on the charts provided earlier. For example, if your optimal weight is 200, your minimum weight would be 190 (200 times 0.95). If your weight falls below this minimum number, increase your calorie consumption. Select foods low in caloric density. The best way to reduce calories is to eat low-starch vegetables such as broccoli and summer squash, which are filling and have relatively few calories, instead of potatoes and rice.
Focus on fiber. Another choice is foods rich in fiber, which provides bulk and texture with no digestible calories. Fiber also has health benefits by lowering cholesterol levels, improving regularity, and reducing the risks of colon cancer. Most vegetables are, of course, high in fiber. There are also many foods designed to be carbohydrate substitutes that use fiber (as well as vegetable protein) to replace the bulk and texture of starch, such as low—carbohydrate cereals and breads.
Caloric Restriction Without the Restriction
A birth control pill that worked by suppressing interest in sex would probably find a limited market. People similarly enjoy the sensual pleasure of eating, so they don’t want that enjoyment restrained either. The solution is to eat a diet that has a very low glycemic load, limits carbohydrates, and is generally low in fats. However, it would still be desirable if we could eat more – perhaps as much as we wanted – and nonetheless enjoy the benefits of caloric restriction and remain slim, like the “lucky” FIRKO mice. So, while medications to control appetite will continue to play an important role, the holy grail of diet drugs is one that lets us eat as much as we want while maintaining an optimal weight.
In the Joslin study, blocking the FIR (fat insulin receptor) gene in the fat cells of mice enabled the mice to eat a lot and remain thin. Why? Since insulin is needed to help fat cells store fat, these animals had less fat and were protected against the obesity that occurs with aging or overeating. They also were protected against the metabolic abnormalities associated with obesity, including type 2 diabetes,” said Dr. C. Ronald Kahn, who headed the study.
Drug developers are currently working on translating these results into human drugs. Such drugs would clearly be blockbusters, and so we can be confident that efforts to develop them will be intense. In biotechnology research conducted by Roger Unger and his colleagues at the University of Texas Southwestern Medical Center, a virus genetically engineered to deliver the gene for the hormone leptin, which controls appetite, was injected into the livers of rats. These rats then produced high levels of the hormone and lost weight. Leptin is normally produced by fat cells, but fat cells develop a resistance to their own leptin. Because it was coming from another organ (the liver), the fat cells remained sensitive to it.
Surprisingly, not only were the fat cells of the animals carrying less fat, but they also had an unusually large number of mitochondria. Normally, fat cells have very few mitochondria; muscle cells, which need a lot of energy, have many. Increasing the number of mitochondria in fat cells is remarkable and had not been seen before. Once perfected, this approach would have the effect of permanently increasing metabolism, thereby maintaining a low weight.
Precose, a prescription starch blocker, should be taken with meals. A more recent prescription starch blocker is Glyset. There are a number of “natural” starch blockers available over the counter; however, we have had mixed results with these products in our own informal tests, which suggest that Precose is more effective than nonprescription starch blockers.
These starch blockers do not block sugar because it doesn’t need to be broken down.
Xenicalis, a prescription drug that, like starch blockers, blocks key digestive enzymes called lipases, which break down fat. Xenical blocks about one-third of the fat consumed from being digested.
Another approach is a “natural” polymer called chitosan, a derivative of shellfish and available in health food stores, although it is less effective than Xenical. Chitosan binds to the fatty acids directly. It can bind up to about six times its own weight in fat, which then becomes indigestible and passes through the Gl tract.
A word of caution: fat blockers will inhibit fat-soluble vitamins, such as vitamin E, so don’t use one within three hours of (before or after) taking fat- soluble supplements. Fat blockers also block the fat-soluble vitamins contained in food as well as healthy fats, such as omega-3 fats and oleic acid If your fat consumption consists primarily of the healthy fats, binding a portion of these fats with a fat blocker may still be acceptable.
More effective calorie blockers, as well as body fat inhibitors, are in the pipeline. In the meantime, there are extensive benefits to restricting calories and maintaining a lower body weight. If you combine moderate caloric restriction with a diet that avoids high-glycemic-load foods, restricts carbohydrates, and is generally low in fat (while emphasizing healthy fats), you will find that you can be slim but still eat plenty of food-and never be hungry.

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