I was practicing Caloric Restriction with Adequate Nutrition (CRAN) fairly intensely for 4 years from 1994 (and more mildly thereafter) in order to extend my lifespan. As indicated in the article "Caloric Intake and Aging" by Dr. Richard Weindruch in the October 2, 1997 issue of THE NEW ENGLAND JOURNAL OF MEDICINE, restricting calories 30-60% (while maintaining adequate nutrition) extends the lifespan of rodents. Both the average and maximum (the mean lifespan of the longest-lived 10%) lifespan are extended 30-60%. This experiment has been repeated on hundreds of diverse species of animals -- including over 200 mammalian species -- with similar results. A conclusive experiment on humans has not been feasible due to our long lifespans, but it seems hard to believe that CRAN would not make us live longer.

The most thorough experiments on the life-extending effects of CRAN are documented in the book THE RETARDATION OF AGING AND DISEASE BY DIETARY RESTRICTION (1988) by Roy L. Walford, MD and Dr. Richard Weindruch (who completed his PhD under Dr. Walford). Dr.  Walford has attempted to make his work accessible to laypeople through his books THE 120-YEAR DIET (1986) and THE ANTI-AGING PLAN (1994). These books explain both theory and practice for adults desiring the health/lifespan benefits of CRAN. Dr. Weindruch has done more to "popularize" the benefits of CRAN among the scientific community.

Despite the extensive evidence of lifespan prolongation by CRAN among many short-lived species, claims are made that such species are more expendable and that their physiological adaptations would not be comparable to long-lived species. To investigate this question, studies have been initiated on rhesus & squirrel monkeys at the National Institute of Health and on rhesus monkeys by Dr. Weindruch at the University of Wisconsin. Squirrel monkeys have a 20-year lifespan and rhesus monkeys have a 40-year lifespan. It is hoped that by studying "biomarkers of aging" (physiologic changes with age) that much can be learned long before the experiments have ended. Unfortunately, verified biomarkers of aging do not exist. In fact, one of the objectives of the experiments is to determine & validate biomarkers [*1].

One of the most promising candidates as a biomarker of aging is insulin resistance. With aging, there is increasing resistance to the effects of insulin, including facilitation of glucose transport into cells. This may be due to glycation (protein cross-linking due to glucose) of insulin receptors. Since protein cross-linking may be an important mechanism of aging, insulin sensitivity & fasting blood glucose may be biomarkers of aging. Both the study at the National Institute of Health [*2] and the study at the University of Wisconsin [*3] have found less insulin resistance in CRAN monkeys when compared to control monkeys.

Inadvertent CRAN experimentation on humans occurred in the Biosphere, when the food available was found to be less than anticipated, although nutritionally adequate. Because Dr. Walford was the physician for the 8-member Biosphere team, he monitored, documented and later summarized the results [*4]. In the first six months, on 1800 calories per day, the Biospherians showed an average 15% weight loss, 18% lower blood glucose, 35% lower blood cholesterol and 18%/21% (systolic/diastolic) lower blood pressure. Although cholesterol & blood pressure are not biomarkers of maximum lifespan, they are biomarkers of average age of death.

I place a great emphasis on the fact that nutrition must be adequate to prevent deficiency disease in order for caloric restriction to work, which is why I use the acronym CRAN. The use of adequate nutrition might seem trivially obvious, but in 1971 the ANNUAL REVIEW OF BIOCHEMISTRY reported [*5] that 24% of the rat studies in the JOURNAL OF NUTRITION contained inadequate amounts of vitamins & minerals. This undoubtedly accounted for a large portion of failures to extend lifespan with calorie restriction. Now no serious gerontologist questions that CRAN can extend lifespan.

Six years ago I weighed 168 pounds, whereas now my weight is closer to 120 pounds. I am between 5'7" and 5'8" tall. My blood pressure has dropped from highs of 130/96 to about 100/70. In the first 3 years of my practicing CRAN there was a 20% drop in my blood glucose, a 47% drop in my blood uric acid, my LDL/HDL cholesterol ratio dropped from 2.0 to 0.86 and my blood triglycerides dropped to one-third of the previous value.

I do not use complicated computer programs to obtain adequate nutrition from foods. I rely on Life Extension Mix and other supplements to provide me with more than adequate nutrition. My breakfast consists of 100 grams of broccoli, 100 grams of strawberries, a spoonful of Herbal Mix and a scoop of Natural Flavor Designer Protein powder blended together in my Vita-Mix blender. This gives me about half of my daily requirement of protein for less than 150 calories. My next meal is at 4 pm, and this is usually some fat-reduced tofu with sweet red pepper and berries (about 200 calories). Most of my calorie-intake is in the evening, beginning 8 pm to 10 pm.

The World Health Organization estimates that a 143-pound male requires 2700 calories/day to maintain weight, and that a 121-pound woman requires 2100 calories. For six months I kept below 1600 calorie/day (below 1400 calories/day for one of those months), although now it is probably more in the range of 1800-2000 calories/day.

I have been health-conscious for as long as I can remember. I began my practice of CRAN almost by accident. I stopped eating meat & pasta and watched the pounds drop away without feeling that I was depriving myself of enough to eat. I still believe that alteration of food choices can do a great deal to reduce calorie intake without any alteration in levels of hunger/satiety. I avoid fat, alcohol & sugar with great diligence. I have, at times, avoided fruits (especially bananas) because of their high sugar content. Now I permit myself to eat strawberries, because they are low in calories and high in phytochemicals. I am also avoiding cereals because these carbohydrate foods provoke too much appetite, and often cause me to "binge". Vegetables are the staple of my diet, with skim milk cheese, defatted tofu, lentils and occasional fruit (usually strawberries). When people or laboratory animals eat a diet high in fiber, they consume fewer total calories [*6].

People often speak of hunger as being a barrier to practicing CRAN, but I think people often eat for reasons other than hunger. People eat out of habit -- because it is "mealtime" (a social ritual). People regularly eat for enjoyment -- to entertain themselves (a popular form of recreation). People eat because of appetite -- something very distinct from hunger. And people eat until they are "full". Eating to satiety is very difficult to avoid, even for me. Resisting the temptation to start eating is much easier than ceasing to eat once eating has begun.

I am not afraid to experience hunger. If a person wants to seriously restrict calories, then will-power and a willingness to experience feelings of hunger must eventually enter the picture. It is remarkable to me how absolutely unwilling people can be to allow themselves to feel even the slightest amount of hunger. Often, all that is needed is to wait a few minutes for the feeling to pass. But even if the feeling does not immediately pass, I think it is a discomfort that a person can learn to live with -- like the necessity of getting up in the morning to go to work, or the engaging in exertions required for exercise. Learning to accept various levels of hunger is like building a muscle. It takes practice.

Nonetheless, I am still trying to find gimmicks I can use to reduce my calorie intake while minimizing my discomfort. Changing eating habits involves "training". Once skim milk tasted like water to me, and I avoided it. I trained myself to drink skim milk, rather than 2%, until I finally accepted skim. Now 2% milk tastes like overly rich cream to me. I have trained myself to eat low-calorie vegetables when my appetite might incline me to eat something else. And I have learned not to buy or keep high-calorie foods in my kitchen.

A very useful practice I have found is to refuse to eat any food that I have not first weighed and calculated the calorie content for. I have a copy of the book FOOD VALUES by Jean Pennington (15th Edition, 1989) from which I have obtained the calories per gram of all the foods I eat. These results are summarized in sheets of paper taped to my cupboard doors. Calculating the caloric content of all eaten foods does a great deal to increase awareness of calories -- and the process is essential for anyone restricting themselves to an upper limit of calories per day. For six months I weighed all my food and calculated calories to ensure that I would not exceed 1600 calories per day.

For a person who is neither gaining nor losing weight, the calories being consumed will equal the calories being burned & excreted. It follows that if a person chooses to reduce calorie intake, weight loss must occur until the reduced calorie intake equals the calories burned & excreted at the new, reduced weight. (A smaller body mass will burn fewer calories in basal metabolism and will require fewer calories for movement.) For this reason, novices to CRAN are constantly asking how much weight they should lose, and how fast they should lose it.

Although much experimentation has been done on the effects of CRAN, there has been little or no experimentation to determine the combined effects of varying rates of weight loss at various ages on the life extending benefits of CRAN. Dr. Walford had made some intuitive guesses about this, but his experience with Biospherians losing an average of 15% of their body weight in six months caused him to decide that weight loss could safely occur more rapidly than he previously thought.

A pound of fat corresponds to about 4,000 calories, whereas a pound of lean tissue (mostly protein) corresponds to less than half that many calories. A dieting fat person is more likely to lose fat than a dieting lean person, everything else being equal. Combining dieting with exercise results in less loss of lean tissue and more loss of fat [*7]. The greatest danger in excessively rapid loss of weight is potassium depletion [*8] and damage-to & loss-of heart muscle, leading to cardiac arrhythmias [*9]. Cardiac arrhythmias have been a major cause of death among anorexics [*10] and among dieters in the late 1970s who used liquid protein diets [*11].

People suffering from anorexia nervosa typically practice caloric restriction without adequate nutrition. Anorexics frequently deplete their electrolytes through self-induced vomiting and through abuse of purgative laxatives. Early liquid protein diets were composed of poor quality protein (collagen, often supplemented with tryptophan). Modern very low calorie diets use high quality protein (like egg albumen) along with carbohydrate to reduce ketosis & electrolyte loss [*12]. Whey protein in the diet should be particularly good for weight-loss because whey is high in branch-chain amino acids, a major component of muscle protein. The mortality rate for modern very low calorie diets is actually lower than that for obese controls [*13]. Adequate nutrition during weight loss will not be the same as adequate nutrition during steady-state caloric restriction.

Although exercise seems advisable to maintain lean tissue during weight loss and to reduce the risk of cardiovascular disease in the general population, it is debatable whether exercise is of benefit for people practicing CRAN. The most careful research on this subject has been the rat studies of John Holloszy at Washington University School of Medicine in St. Louis. His experiments seemed to indicate that aerobic exercise actually reduced the benefits of CRAN [*14]. But in his most recent experiment on the interaction of CRAN and exercise [*15], Holloszy found no difference between the survival curves of exercising and non-exercising CRAN rats. He speculated that his previous results may have been due to a health problem in the rats under study.

If exercise is of neither benefit nor harm to the practice of CRAN, why do it? One reason I exercise is to maintain physical strength & endurance. I also exercise to reduce my dependence on diet for calorie restriction (see Holloszy [*14]). Yet another reason for my exercising is to lift my spirits. Many of those practicing CRAN complain of weakness, lack of energy and depression. I think exercise has much to do with why I rarely experience those symptoms. However, I sometimes feel sluggish & dispirited in the midafternoon, possibly due to low blood sugar. Instead of taking a lunch-break, I take an exercise-break. Afterwards, I usually feel terrific.

I also think that CRAN plus moderate exercise can extend lifespan beyond what can be achieved by CRAN or exercise alone. For a person practicing CRAN, I think the beneficial effects of exercise on the health of the cardiovascular system, bones, muscles, etc. is negated by the harmful effects of free-radicals generated by exercising [*16]. I think that there is substantial evidence that the use of anti-oxidants -- Vitamin E in particular -- greatly reduces free radical damage due to exercise [*17]. But the Vitamin E should be taken with kelp or another Vitamin K source to avoid the danger of inhibited blood clotting [*18]. An experiment which I would like to see done, which has not been done, is a study of the combined effects of CRAN, Vitamin E, Vitamin K and exercise.

Many people will say that the known hunger & discomfort of CRAN is not worth the hypothetical benefit. I am an ardent life-extensionist so the prospect of extending my lifespan has driven me to a very rigorous practice of CRAN. However, many others practice CRAN to a more moderate extent with the expectation of more moderate benefits. Each person can gage the level of effort they are willing to expend, knowing that the payoff is likely to be commensurate to the effort.

Even if it were true that the extension of maximum lifespan seen in CRAN experimental animals is not applicable to human beings, there is much evidence that CRAN will extend the average lifespan of people. Death by cardiovascular disease shortens human life by an average of 13 years. It has long been known that cardiovascular mortality is lowest among those who are leanest [*19]. For this reason, CRAN may actually be of more benefit to humans than to rodents, since rodents usually die of cancer rather than cardiovascular disease. Additionally, cardiovascular health will likely reduce the rate of vascular dementia, the second most common cause of dementia in the elderly (after Alzheimer's Disease).

15% of people over age 60 develop maturity-onset diabetes, usually due to excessive calorie intake. The likelihood of developing diabetes doubles with each decade of life, and also doubles with every 20% gain of body weight above average. Earlier cancer studies had shown 10% underweight to be a lesser risk factor for mortality than 20% underweight [*20]. But more recent studies, which carefully corrected for smoking & underlying disease, have shown that the leanest people are the least likely to die [*21].

Psychologically, my practice of CRAN has been very beneficial for me. For years I had been afraid to diet because of the media claims that "diets don't work" and that yo-yo dieting is more harmful to health than maintenance of a steady weight. The claim about the health hazard of yo-yo dieting (for non-smokers, at least) has been disproven [*22].

Only 5% of dieters keep their pounds off for more than 5 years. But most dieters are not highly motivated life-extensionists. Most dieters are primarily concerned about their appearance, often only to specific people at specific times. I have kept my weight off for 3 years -- primarily backsliding due to traveling -- but eventually "recovering". I take a great deal of pride not only in my trim appearance, but in my will-power. I do binge from time-to-time, which is not good for my self-esteem, but this has not undermined my overall results.

Most successful dieters have achieved their success only after repeated attempts and much practice. People who successfully keep weight off usually do so by making permanent life-style changes, by avoiding dietary fats, by weighing themselves regularly, and by regular exercise. I do all of these. The dietary alterations made the biggest difference in my weight, however, because my exercise program (3 aerobic workouts per week) has not changed in the last decade. Learning about food and about how I can control my eating habits has been a fascinating process.

Another benefit is the fact that I seem to require less sleep, something other CRAN practitioners have noticed also. For two years I had no sickness of any kind, not even my annual Christmas cold/flu. Nor do I feel that I lost the pleasures of food. In fact, I have never enjoyed food so much as since I have adopted the practice of CRAN. I eat less, but what I do eat I enjoy immensely. This enhanced appetite has also made it easier for me to learn to like foods such as low-fat tofu.

To me it seems very likely that CRAN will reduce the rate at which I age. The lower calorie demands of my lower weight have translated into my demonstrably lower blood glucose levels. Cross-linking of proteins by blood sugars normally results in more fibrous connective tissues and hardening of the arteries, among other symptoms. This is why diabetes often resembles accelerated aging. Moreover, by requiring less energy (fewer calories), my body's mitochondria are generating fewer free-radicals to damage DNA and other cellular structures. I believe reduced free-radical production provides much better protection against cellular damage & aging than attempting to quench existing free-radicals with anti-oxidants.

CRAN is not without its hazards, however, above and beyond the inability to indulge all the pleasures of the appetite. Nearly all CRAN practitioners experience an increased sensitivity to cold, particularly in the extremities. My feet are usually cold if I take no precautions. I wear at least 2 or 3 pairs of heavy socks -- even when I am sleeping.

Another hazard is hemorrhoids. During various stages of my food restriction experiments I noticed that my stools would become small, dry and hard. Eventually I got hemorrhoids. I now know that adequate nutrition for CRAN must include adequate fiber. Eating many vegetables doesn't necessarily guarantee adequate fiber. The best fiber to prevent hemorrhoids is a mixture of psyllium & wheat bran. This mixture has the added benefit of having been shown to reduce the incidence of colon cancer in experimental animals to a quarter of that seen in controls [*23]. Colon cancer is second only to lung cancer as a cause of cancer death in humans.

The very worst hazards I experienced in practicing CRAN, however, were toward the end of my 6-month period on fewer than 1600 calories per day. My weight had dropped below 115 pounds and I was experiencing lightheadedness, physical weakness, periodic cardiac acceleration and gastrointestinal pains. (My lightheadedness was so extreme at one point that I fainted -- not while I was driving, luckily.) I experienced my first flu in over 2 years, and had difficulty shaking it off. I was down to 112 pounds when it was time for my annual physical examination.

My 15-hour fast in preparation for my examination caused me great discomfort, possibly including symptoms of hypoglycemia (low blood sugar). When my physician put me on an EKG he found bigeminal rhythm -- extrasystoles (heartbeat irregularities). He didn't rush me to the hospital, but he did warn me that I should gain some weight. Extrasystoles are not usually life-threatening, but they can be. I immediately went on an eating binge. It took me a while to regain my stability and pursue a more "moderately stringent" version of CRAN. Currently, my target weight is 120 pounds, and I rarely go above 123.

Laboratory animals (and people living in Biosphere) are in protected environments. People who are living workaday lives may be subject to stresses and vulnerable to conditions which could make hypoglycemia or weight-loss due to a disease condition more dangerous. I believe that keeping my weight between 119 and 123 pounds provides me with a certain buffer against such events. I also suspect that there may be an important difference between CRAN which is imposed upon laboratory animals and (to a lesser extent) upon Biospherians, and between CRAN, which is a voluntary practice. Voluntary CRAN can create psychological stress. Beyond a certain intensity this stress may be physically damaging, through secretion of excessive amounts of stress hormone (cortisol). Hypercortisolism is seen in CRAN animals [*24] and in anorexics [*25]. One theory of aging makes a strong case for the idea that stress & glucocorticoids play a key role [*26].

Another thing I learned from my physical examination was that my testosterone levels were well below the normal range. I had noticed a dramatic drop in my libido and was well aware that CRAN animals typically show reduced levels of sex hormones. Female anorexics often stop having periods. A silver lining to my low testosterone levels, however, is the greatly reduced risk of prostate cancer. My Prostate Specific Antigen (PSA) was 1.5 ugm/L, well below the normal limit of 4.0.

Sex hormones are produced from DHEA, which is produced from cholesterol. My blood DHEA (as measured by the Life Extension Foundation) had been equal to the level of an average 95-year-old -- which is pretty low for a middle-aged man like me. After learning that my testosterone was also low, I began taking 15 mg of DHEA 3 times daily, in the hope that my DHEA & testosterone levels could increase. My libido has increased somewhat, and a more recent Life Extension Foundation measurement of my DHEA has shown me to be at the level of an average 75-year-old. DHEA is known to oppose the actions of cortisol [*27], so this might be a way to oppose the "stress response" and boost my immune system. I plan to increase my DHEA and see what my blood levels of cortisol & testosterone are at my next physical examination.

My practice of CRAN has had some difficult social consequences. I have been told that I look like a cancer victim and some people have suspected that I have AIDS. This was particularly the case when I was losing weight. Now that people have adjusted to the idea that I am a thin person, I don't hear these comments. But the fact that so many social activities center around food can create problems. I don't want to insult people who prepare food for me and I don't want to cut myself off entirely from dinner parties. As long as I keep the frequency of social dinners to less than once per week I don't think they overly compromise my CRAN program.

I make a similar allowance for my binges, which are often the product of excessive stress. Rigorous CRAN is itself a stress, and when added to other stresses I sometimes feel the need for relief. Most of the time, however, the stress of hunger is moderate, and I actually gain a sense of satisfaction & accomplishment by experiencing it. I think about food frequently, which could be distracting, but I have learned to appreciate my fascination with food. I have learned a great deal about food, physiology and nutrition in conjunction with my experiments on myself.

For nearly 3 years I have been an active contributor to an Internet list server group of people who are practicing CRAN (more often called "CR"). Until last year, there were monthly postings which summarized data about the participants, including height, weight, estimated "set-point" and calories consumed per day. My practice of CRAN was among the more stringent (but by no means the most stringent) of the group. Comparisons are difficult, however, because bone thickness & muscular development may be different for two individuals of the same height & weight. Additionally, some people are "naturally thin". Walford & Weindruch observed that mice on the same level of calorie restriction may have different weights, and that the heavier animals live longer. Dr. Walford has written that extended lifespan is less associated with a low body weight and more associated with how much an animal (or person) is below the weight they would have if they ate freely (with no calorie restriction). This "natural weight" is called the "set point". A naturally thin person will not have the life-extension benefits as a person of the same height & weight who is below the "set-point" due to the practice of CRAN.

About a year ago, someone conducted a survey of 14 people on the Internet list in order to determine frequency of "side effects", both positive and negative. About 50% reported low moods or depression and about 30% reported muscular weakness. These symptoms were greater in the "higher-level" practitioners than in the "mild to moderate" practitioners. At my current level of "moderately rigorous" CRAN (120 pounds), I experience none of the above symptoms. Nor do I experience the drop in energy reported by 40% of the "high level" participants (most of the "mild to moderate" reported normal or increased energy). I believe this is because I exercise and take supplements.

All participants reported greater sensitivity to cold weather. Eight respondents reported lower body temperature, averaging 97.0°F (36.1°C). Half reported a decreased sex drive and about 30% reported hemorrhoids.

On the positive side, most reported reduced sleep requirements as well as normal or increased alertness & clarity.

There is a distinct bias on that list server group against taking supplements. The belief seems to be that (aside from a multivitamin tablet to ensure adequate nutrition), a person practicing CRAN can gain no further life extension benefits from supplements. When someone argues for the benefits of a supplement based on animal experiments or human studies, others will reply that the results had not been obtained from CRAN animals or humans. This is true, but there have been precious few lifespan studies on supplements at all, and nearly none on CRAN animals.

There was, however, an experiment which studied the effects of an anti-oxidant combination on CRAN (20% calorie restricted) mice. The experiment was conducted by Dr. Steven B. Harris under the auspices of Walford & Weindruch [*28]. The anti-oxidants actually negated the effects of CRAN. While the unsupplemented CRAN mice showed the usual extension of average & maximum lifespan, the CRAN mice taking anti-oxidants had survival curves matching those of the control animals. Although ethoxyquin is known to cause lesions in liver & kidney, previous experiments had shown extension of average lifespan in short-lived strains of mice that had early incidence of disease. In this experiment, however, there was no difference in average or maximum lifespan between the two groups of non-CRAN animals, one group of which was taking the anti-oxidants. Liver damage was seen in the CRAN animals receiving anti-oxidants. Kidney disease is the leading cause of death in the CRAN rats in Hollszy's experiments [*14]. I am suspicious of the choice of ethoxyquin as test anti-oxidant, and would rather have seen Vitamin E tested. Dr. Harris did a later experiment with Dr. Stephen Coles in which they found a 20% increase in average lifespan for CRAN (10-15% calorie restricted) mice supplemented with Co-enzyme Q-10 [*29].

Aside from lack of exercise, I suspect that many CRAN practitioners suffer from weakness, depression and lack of energy as a consequence of vegetarianism. Most people attempting CRAN are vegetarians or near-vegetarians. In some cases there may be problems with Vitamin B12 deficiency. But there may also be a problem due to carnitine, which is known to be significantly lower in the diet & bloodstream of vegetarians [*30]. Carnitine protects heart muscle from ischemic damage and has been used to treat chronic fatigue syndrome [*31]. The Acetyl-L-Carnitine form, of which I take 500 mg every morning, crosses the blood-brain barrier, is neuroprotective [*32] and has been used as an effective treatment to slow the progress of Alzheimer's Disease [*33].

I think that supplements like DHEA may complement CRAN, and that anti-oxidants are of particular benefit for reducing free-radicals from exercise & pollution. I have been taking Deprenyl, CoEnzyme Q10, DHEA, Tocopherols, Melatonin, Ginko & DMAE, Acetyl-L-Carnitine (especially good for vegetarians) and essential fatty acid & multi-mineral capsules, in addition to my Life Extension Mix. I take my supplements with my meals -- at 8 am, 4 pm and midnight. In fact, my mealtimes are based on my attempt to take my supplements with food and ensure even blood levels of my supplements (especially the DHEA and water-soluble vitamins). Arguments over supplements and other issues on the Internet list server caused me to start my own list server group for people interested in practicing CRAN.

I have found a list server to be a very valuable forum for the sharing of information of interest for people attempting to practice CRAN. Topics of discussion have included the use of artificial sweeteners, the relevance of glycemic index, the importance of variety in diet, the value of fasting, mechanisms by which CRAN works, the personality of CRAN practitioners, breadmaking, patterns of eating to reduce hunger, the value of uncooked food, the role of exercise, etc.

I believe that most people can practice some degree of CRAN with few or none of the problems I have had if they are willing to learn from my experiences -- particularly those I have just described. I doubt that many are willing to go to the extremes that I have gone to. But I think that a "mild to moderate" practice of CRAN could be a way for most people to see present improvement in health and an extended life in the future.

    ** NOTE ON GLUCOSE: Multiply by 18.0 to convert mmol/L to mg/100mL (because glucose is 180.0 g/mol)

    *** NOTE ON CHOLESTEROL: Multiply by 39 to get an approximate conversion of MMOL/L to MG/DL

My Current Health Regimen -- Exercise, Diet, Supplements

The CRAN Man
Ben Best at 120 pounds

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FOOTNOTES

• [*1] "Dietary Restriction of Adult Male Rhesus Monkeys: Design,
• Methodology, and Preliminary Findings From the First Year of Study"
• Joseph W. Kemnitz, et.al.
•    JOURNAL OF GERONTOLOGY (BIOLOGICAL SCIENCES) 48(1):B17-B26 (1993)

• [*2] "Diet restriction in rhesus monkeys lower fasting and
• glucose-stimulated glucoregulatory end points" Mark A. Lane, et.al.
•    AMERICAN JOURNAL OF PHYSIOLOGY 268:(5 Part 1):E941-E948 (1995)

• [*3] "Dietary restriction increases insulin sensitivity and lowers
• blood glucose in rhesus monkeys" Joseph W. Kemitz, et.al.
•    AMERICAN JOURNAL OF PHYSIOLOGY 266:(4 Part 1):E540-E547 (1994)

• [*4] "The calorically restricted, low-fat, nutrient dense diet in
• Biosphere 2 significantly lowers blood glucose, total white cell
• count, cholesterol and blood pressure in humans" Roy L. Walford, et.al.
•    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE U.S.A.
•    89:11533-7 (1992)
• "'Biosphere Medicine' as Viewed From the Two-Year First Closure
• of Biosphere 2" Roy L. Walford, et.al.
•    AVIATION, SPACE, AND ENVIRONMENTAL MEDICINE 67(7):609-617 (1996)

• [*5] "Nutritional Methodology in Metabolic Research with Rats"
• Heather Greenfield & George M. Briggs
•    ANNUAL REVIEW OF BIOCHEMISTRY 40:549-572 (1971)

• [*6] "The Effect of Dietary Cellulose on Life Span and Biochemical
• Variables of Male Mice" G.C. Kokkonen & C.H. Barrows
•    AGE 11(1):7-9 (1988)
• "Satiation, Satiety and the Action of Fibre on Food Intake"
• J.E. Blundell & V.J. Burley
•    INTERNATIONAL JOURNAL OF OBESITY (Suppl.1) 11:9-25 (1987)
• "The effects of high and low energy density diets on satiety,
• energy intake, and eating time of obese and non-obese subjects"
• Karen H. Duncan, et.al.
•    AMERICAN JOURNAL OF CLINICAL NUTRITION 37:763-767 (1983)

• [*7] "Effects of dieting and exercise on lean body mass, oxygen
• intake, and strength" Konstantin Pavlou, et.al.
•    MEDICINE AND SCIENCE IN SPORTS AND EXERCISE 17:466-471 (1985)
• "Resistance weight training during caloric restriction enhances
• lean body weight maintenance" Douglas L. Ballor, et.al.
•    AMERICAN JOURNAL OF CLINICAL NUTRITION 47:19-25 (1988)

• [*8] "Relation of Electrolyte Disturbances to Cardiac Arrhythmias"
• Charles Fisch
•    CIRCULATION 47:408-419 (1973)

• [*9] "Effects of Self-Induced Starvation on Cardiac Size and Function
• in Anorexia Nervosa" John S. Gottdiener, et.al.
•    CIRCULATION 58:425-433 (1978)

• [*10] "Anorexia nervosa and bulemia nervosa" Kathryn J. Zerbe
•    POSTGRADUATE MEDICINE 99(1):161-169 (1996)

• [*11] "Sudden death associated with very low calorie weight
• reduction regimens" Harold E. Sours, et.al.
•    AMERICAN JOURNAL OF CLINICAL NUTRITION 34:453-461 (1981)
• "Sudden, Unexpected Death in Avid Dieters Using the
• Liquid-Protein-Modified-Fast Diet" Jeffrey M. Isner, et.al.
•    CIRCULATION 60(6):1401-1412 (1979)

• [*12] "The Historical Development of Very Low Calorie Diets"
• A.N. Howard
•    INTERNATIONAL JOURNAL OF OBESITY 13 (Suppl.2):1-9 (1989)

• [*13] "Very Low Calorie Diets"
• National Task Force on the Prevention and Treatment of Obesity
•    JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION 270:967-974 (1993)

• [*14] "Effects of voluntary exercise on longevity of rats"
• John O. Holloszy, et.al.
•    JOURNAL OF APPLIED PHYSIOLOGY 59(3):826-831 (1985)
• "Interaction between exercise and food restriction: effects on longevity of male rats" J.O. Holloszy & K.B. Schechtman
•    JOURNAL OF APPLIED PHYSIOLOGY 70(4):1529-1535 (1991)

• [*15] "Mortality rate and longevity of food-restricted exercising
• male rats: a reevaluation" John O. Holloszy
•    JOURNAL OF APPLIED PHYSIOLOGY 82(2):399-403 (1997)

• [*16] "Biochemical Mechanisms for Oxygen Free Radical Formation
• During Exercise" Bertil Sjodin, et.al.
•    SPORTS MEDICINE 10(4):236-254 (1990)

• [*17] "Vitamin E prevents exercise-induced DNA damage"
• Andrew Hartmann, et.al.
•    MUTATION RESEARCH 346:195-202 (1995)
• "Dietary supplementation of Vitamin E protects heart tissue from
• exercise-induced oxidant stress" Charles T. Kumar, et.al.
•    MOLECULAR AND CELLULAR BIOCHEMISTRY 111:109-115 (1992)
• "Exercise, Oxidative Damage and Effects of Antioxidant Manipulation"
• Eric H. Witt, et.al.
•    JOURNAL OF NUTRITION 122:766-773 (1992)

• [*18] "The Effect of Intravenous Vitamin E and Menadiol Sodium
• Diphosphate on Vitamin K Dependent Clotting Factors" Lawrence Helson
•    THROMBOSIS RESEARCH 35:11-18 (1984)
• "Study on the effect of megavitamin E supplementation in man"
• Alan C. Tsai, et.al.
•    AMERICAN JOURNAL OF CLINICAL NUTRITION 31:831-837 (1978)

• [*19] "Thinness and Mortality" Stephen Sidney, et.al.
•    AMERICAN JOURNAL OF PUBLIC HEALTH 77:317-322 (1987)
• "Body mass index and patterns of mortality among Seventh-day
• Adventist men" Kristian Lindsted, et.al.
•    INTERNATIONAL JOURNAL OF OBESITY 15:397-406 (1991)

• [*20] "Variations in Mortality by Weight Among 750,000 Men and
• Women" E.A. Lew & L. Garfinkle
•    JOURNAL OF CHRONIC DISEASES 32:563-576 (1979)

• [*21] "Body Weight and Mortality among Women" JoAnne E. Manson, et.al.
•    NEW ENGLAND JOURNAL OF MEDICINE 333(11):677-685 (1995)
• "Body weight and mortality: a 27-year follow-up of middle-age men"
• I.M.Lee, et.al.
•    JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION 270:2823-2828 (1993)

• [*22] "Association of Weight Loss and Weight Fluctuation with
• Mortality Among Japanese American Men" Carlos Iribarren, et.al.
•    NEW ENGLAND JOURNAL OF MEDICINE 333(11):686-692 (1995)

• [*23] "Potential synergism between wheat bran and psyllium: enhanced
• inhibition of colon cancer" O. Alabaster, et.al.
•    CANCER LETTERS 75:53-58 (1993)

• [*24] "Chronic Food Restriction and the Circadian Rhythms of
• Pituitary-Adrenal Hormones, Growth Hormone and
• Thyroid-Stimulating Hormone" A. Armario, et.al.
•    ANNALS OF NUTRITION AND METABOLISM 31:81-87 (1987)

• [*25] "Abnormal Hypothalamic-Pituitary-Adrenal Function in Anorexia
• Nervosa" Philip W. Gold, et.al.
•    NEW ENGLAND JOURNAL OF MEDICINE 314:1335-1342 (1986)

• [*26] "The Neuroendocrinology of Stress and Aging: The
• Glucocorticoid Cascade Hypothesis" Robert M. Sapolsky, et.al.
•    ENDOCRINE REVIEWS 7:284-301 (1986)
•  STRESS, THE AGING BRAIN AND MECHANISMS OF NEURON DEATH
•           by Robert M. Sapolsky (1992)

• [*27] "Anti-glucocorticoid effects of dehydroepiandrosterone (DHEA)"
• Mohammed Kalimi, et.al.
•    MOLECULAR AND CELLULAR BIOCHEMISTRY 131:99-104 (1994)

• [*28] "Dietary Restriction Alone and in Combination with Oral,
• Ethoxyquin/2-Mercaptoethylamine in Mice" Steven B. Harris, et.al.
•    JOURNAL OF GERONTOLOGY (BIOLOGICAL SCIENCES) 45(5):B141-B147 (1990)

• [*29] "Co-Enzyme Q-10 and Life Extension" L. Stephen Coles & Steven
• B. Harris in ADVANCES IN ANTI-AGING MEDICINE, Volume 1, Dr. Ronald
•  M. Klatz, Editor (1996)

• [*30] "Carnitine status of lactovegetarians and strict vegetarian
• adults and children" Kenneth A. Lombard, et.al.
•    AMERICAN JOURNAL OF CLINICAL NUTRITION 50:301-306 (1996)

• [*31] "Carnitine and Its Derivatives in Cardiovascular Disease"
• Michael A. Arsenian
•    PROGRESS IN CARDIOVACULAR DISEASES 40(3):265-286 (1997)

• [*32] "A Cluster Analysis Study of Acetyl-L-Carnitine Effect on
• NMDA Receptors in Aging" Massimo Castorina, et.al.
•    EXPERIMENTAL GERONTOLOGY 28:537-548 (1993)

• [*33] "Acetyl-L-Carnitine: A Drug Able to Slow the Progress of
• Alzheimer's Disease?" A. Carta & M. Calvani
•    ANNALS NEW YORK ACADEMY OF SCIENCES 640:228-232 (1990)

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