Modulation of the Aging Process Using the Zone Diet

written by Barry Sears, PhD.

distributed and endorsed by James J. Romano, M.D.

Aging is associated with pre-mature mortality caused by the breakdown in physiological communication, much of which is controlled by hormones. Thus, aging can be viewed as decreasing hormonal control over those physiological processes necessary for a maximum life span. During the aging process, the levels of many hormones will decrease. However, other hormones will increase with age, in particular insulin and eicosanoids. Elevated levels of these two hormones can be modified by the appropriate diet to be brought into an appropriate zone consistent with a reduction of premature mortality.

Introduction

It is increasingly apparent that 21st-century medicine will emphasize the role of hormonal control, especially in altering the aging process. This should not be surprising when you consider that hormones are the primary messengers of biological information, and the quantity and quality of that information determines how well the body ultimately functions. One of the major problems inherent in anti-aging medicine is the lack of appropriate definitions for this new field. Obviously, such definitions must be more quantifiable than simply looking younger and feeling better. I believe that an appropriate definition for anti-aging medicine is the reduction of premature mortality. Such a definition sets the foundation for evidence-based research to be conducted that conclusively determines whether or not a proposed anti-aging intervention will have a real impact on longevity. Since the primary cause of premature mortality in the Western world is cardiovascular disease, the reduction of those risk factors that have the greatest predictive value for the development of future cardiovascular disease become excellent clinical end points to judge the efficacy of any proposed anti-aging intervention. Much of current anti-aging research is focused on the role of hormone replacement because those hormones can be restored by pharmaceutical intervention. However, the other hormones that actually increase as we age can only be reduced by dietary intervention. It is those hormones, primarily insulin and eicosanoids that are the ones that play a key role in the aging process because of their impact on cardiovascular disease (1,2). Therefore, the goal of an appropriate anti-aging diet is one that brings these hormone levels into a therapeutic zone that is neither too high nor too low and is consistent with optimal health. This is what I term the Zone.

Physiological Description of the Zone

This Zone is not some mystical place or concept, since it can easily be measured and quantified by blood testing. Furthermore the boundaries of this Zone are based upon data derived from prospective studies on the development of cardiovascular disease. Based on such prospective human studies, it is apparent that the three best predictors of future cardiovascular risk are hyperinsulinemia (3,4), an increased triglyceride-to-HDL cholesterol (TG/HDL) ratio (5,6), and an increased ratio of arachidonic acid (AA) to eicosapentaenoic acid (EPA) in the plasma phospholipids(7). The first two risk factors are related to elevated insulin levels, and the last is related to increased eicosanoid levels. The TG/HDL ratio is a surrogate marker for hyperinsulinemia, thus explaining why prospective studies link both of these parameters with increased likelihood of cardiovascular mortality. Decreasing insulin lowers the TG/HDL ratio, which results in a corresponding decrease in the number of small, atherogenic LDL particles (8). It is also increasingly apparent that cardiovascular disease also has a significant inflammatory component associated with its incidence (9,10). This can be measured by non-specific markers of inflammation such as C-reactive proteins. However, since inflammation is an eicosanoid-mediated event, it can be measured more directly by the ratio of AA/EPA in the plasma phospholipids. Pro-inflammatory eicosanoids are derived from AA, whereas anti-inflammatory eicosanoids are derived from EPA. Thus the AA/EPA ratio in the blood will provide direct information on the precursor balance of both inflammatory (AA-derived) and anti-inflammatory (EPA-derived) eicosanoids. In intervention trials with cardiovascular patients, the reduction of the AA/EPA ratio resulted in dramatic reductions in cardiovascular mortality (6,11). This new understanding on the role of the inflammatory process helps to explain why any drug therapy that reduces inflammation, such as aspirin (12) and even the statins (13,14), have such a significant impact on reducing cardiovascular mortality because of their reduction of systematic inflammation. Therefore, any proposed anti-aging intervention should definitely demonstrate reduction of these risk parameters of lowered insulin level or decreased TG/HDL ratio, and a lowered AA/EPA ratio. In Table 1, I have listed some of the levels, which are consistent with reduced premature cardiovascular mortality.

Table 1. Clinical Guidelines that Define the Zone
 

In addition, more than 40 years of gerontology research has identified several universal markers of human aging that must also be reversed with an appropriate intervention if they can be touted as useful in anti-aging medicine. These biological markers of aging are shown in Table 2.

Table 2. Universal Markers of Aging
 

Each of these markers is directly or indirectly associated with changes in insulin or eicosanoid levels. For example, elevated insulin levels precede the accumulation of excess body fat (15,16). Therefore, an age-related increase of insulin would result in the incidence of obesity. In addition, elevated insulin decreases glucose tolerance (by increasing insulin resistance), and also inhibits the release of growth hormone from the pituitary gland that would result in decreased muscle mass. Increased eicosanoid levels will increase blood pressure, and decrease aerobic capacity by decreasing blood flow to the lungs. If those biological markers of aging, along with the appropriate changes in blood chemistry can be reversed through an anti-aging intervention, then dissociation of biological age from chronological age becomes a real possibility. Since these biological markers of aging are strongly associated with hormones that can be altered by the diet, then it is likely that dietary intervention should become the first line of treatment for any anti-aging program.

Dietary Approaches to Reach the Zone

The only known "drug" to increase maximum lifespan is calorie restriction. Calorie restriction has also been shown to reverse both the risk factors of premature cardiovascular mortality and the biological markers of aging (2). Bear in mind that calorie restriction is not malnutrition, because it must also supply adequate levels of vitamins, minerals and essential amino and fatty acids. However, if calorie consumption is decreased by some 30-40% compared to ad libitum consumption, then not only is maximum lifespan increased, but a wide variety of physiological markers associated with aging are also modified (see Table 3).

Table 3. Physiological Changes Induced by Calorie Restriction
 

The physiological changes associated with the calorie restriction are exactly those that are the stated goals of many proponents of anti-aging medicine. However, restricting calories must also be accomplished in the context of improved insulin control. This is why the protein-to-carbohydrate ratio at each meal is critical to maintain insulin levels. Finally, the benefits of calorie restriction can only be achieved if the diet is one characterized without constant hunger or deprivation. This will only be achieved if a constant level of blood sugar is being maintained, which is also a consequence of stable insulin levels, which are controlled by the protein-to-carbohydrate ratio at every meal.

The Zone Diet

The Zone Diet was developed to reduce elevated insulin and eicosanoid levels while maintaining calorie restriction without hunger or deprivation. The Zone Diet consists of three distinct parts. The first is the consistent control of the protein-to-carbohydrate ratio at each meal to lower elevated insulin levels. The second is supplementation with high-dose fish oil (rich in EPA) to alter eicosanoid balance. And the third is the restriction of total calorie intake, but without hunger or deprivation, to promote the physiological benefits of calorie restriction. Surprisingly, the effort by the patient to follow the Zone Diet is quite simple, requiring only the use of what I term the "hand-eye" method. At each meal, a person only eats enough low-fat protein (fish, poultry, low-fat dairy products, egg whites, or soy imitation meat products) that they can fit on the palm of their hand. This would be about 3 oz. (20 grams of protein) for a typical female, and about 4 oz. (30 grams of protein) for a typical male. Then they would divide their plate at each meal into three sections. One third of the plate would contain the appropriate amount of low-fat protein (20-30 grams), and the other two-thirds of the plate would be filled to overflowing with fruits and vegetables (this would be the equivalent of 3-5 servings of fruits and vegetables). Then they would add a dash (3-5 grams) of heart-healthy monounsaturated fat. That described meal will control insulin levels for the next four to six hours. The only trick for the patients is to continue to make all their meals in the relatively same proportions on a lifetime basis. This would mean having a person consume between 10-15 servings of fruits and vegetables per day. Although this appears to be a formidable volume of food, the low carbohydrate density of fruits and vegetables ensures that excess insulin is not secreted at each meal since the absolute amounts of carbohydrates being consumed are restricted. In addition, the calorie content of such a meal would be 30-40% less than typically consumed because of the lowered glycemic load coming from the restriction of high-density carbohydrates such as breads, pasta, and starches. In addition, those levels of fruits and vegetables would provide massive levels of vitamins, minerals, and fiber. The final component of the Zone Diet is to supplement the diet with a suitable amount of pharmaceutical-grade fish oil providing 2-5 grams of long-chain Omega-3 fatty acids. This would provide the necessary long-chain essential fatty acids, such as EPA, required to modulate the AA/EPA ratio.

The reason why there is no hunger or deprivation on the Zone diet (even though it is a calorie-restricted diet) is because of blood sugar stabilization. This can only be achieved when the secretion of insulin (stimulated by the dietary intake of carbohydrates) is appropriately counter-balanced by the secretion glucagon (stimulated by the dietary intake of protein). Insulin drives down blood sugar levels, whereas glucagon restores blood sugar levels. The balancing of this hormonal system by the diet ensures blood sugar maintenance for the 4-6 hour postprandial period. In essence, the goal of the Zone Diet is to maintain both insulin and glucagon within a therapeutic zone that is neither too high, nor too low. If the ratio of protein to carbohydrate in the diet is too low, then excess insulin will be secreted thereby driving down blood sugar and creating hunger. On the other hand, if the protein-to-carbohydrate ratio is too high, excess glucagon will be secreted that can generate a state of ketosis. Therefore, the ideal protein-to-carbohydrate ratio would be in a range that is just beyond that which would generate ketosis, but less than that which would create hyperinsulinemia. My research indicates that the appropriate protein-to-carbohydrate ratio to maintain insulin in the Zone is greater than 0.5 but less than 1.0. Such a mathematical relationship also allows for a more precise definition of high-carbohydrate and high-protein diets. Using this definition, a high-carbohydrate diet would be one that contains more than twice as many grams of carbohydrates compared to grams of protein (a protein-to-carbohydrate ratio of less than 0.5). A high-protein diet would contain more protein than carbohydrate (a protein-to-carbohydrate ratio greater than 1.0). The Zone Diet maintains the protein-to-carbohydrate ratio between these two extremes.

Finally, the Zone Diet also restricts Omega-6 fatty acids (by using primarily monounsaturated fats in the meals) and increasing the levels of long-chain Omega-3 fatty acids by supplementation with pharmaceutical-grade fish oils rich in EPA. This results in a significantly lowered AA/EPA ratio. Recent work from Harvard Medical School has confirmed the ability of the protein-to-carbohydrate ratio found in the Zone Diet to favorably alter the hormonal responses of both insulin and glucagon compared to diets such as the USDA or American Heart Association diets (17,18). Using a cross over protocol employing isocaloric diets, hyperinsulinemic adolescents (17) or overweight adults (18) were provided with meals consisting of different protein-to-carbohydrate ratios. The Zone Diet demonstrated a decreased insulin response and elevated glucagon response with the result that 20-25 percent fewer calories were consumed at the next meal (17) or at the end of the study period (18). This focus on maintaining hormonal control makes it possible to restrict total calories without hunger or deprivation. Other studies, also using isocaloric protocols, have demonstrated that maintaining the same protein-to-carbohydrate ratio advocated on the Zone Diet improves lipid profiles (19) and increases the rate of fat loss (20) when compared to high-carbohydrate diets under isocaloric conditions.

Diabetics have double the rates of cardiovascular mortality and all-cause mortality (21). Thus reducing risk factors associated with diabetics will also have a significant impact on longevity. My own studies with Type 2 diabetics (that account for more than 90 per cent of all diabetics) confirms the success of using all three components of the Zone Diet (insulin and eicosanoid control coupled with calorie restriction) to generate a significant reduction of those risk factors (hyperinsulinemia and glycosylated hemoglobin) associated with future adverse events in Type 2 diabetes.

The results of one six-week trial with Type 2 diabetics following the Zone Diet are shown in Table 4.

Table 4. Effects of Zone Diet in Type 2 Diabetics (n=68)
 

As can be seen from Table 4, the risk factors in the Type 2 diabetic patients following the Zone Diet that are associated with premature development of diabetic complications and increased cardiovascular mortality were reduced with an extraordinarily high degree of statistical significance.

Summary

In the final analysis, anti-aging medicine will ultimately be focused on hormonal modulation that results in the reduction of those risk factors that are the most predictive of premature cardiovascular mortality. The necessary first step is the reduction of those hormones that increase as we age (insulin and eicosanoids) by dietary intervention. Does this mean that hormonal replacement has no impact in anti-aging medicine? No, but without an appropriate hormonal baseline established with the Zone Diet, many of the potential benefits hoped for with hormone replacement therapy may not be observed. All hormonal replacement should follow this basic rule: start low and go slow. The greater hormonal control achieved by application of the Zone Diet, the less hormonal replacement will be required to reach the Zone as determined by blood testing. It is in that Zone of hormonal balance, which will ultimately be the key to evidence-based, anti-aging medicine.

References

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