The use of and diet, habits and supplements
to prevent medical problems and slow the aging process.

"To lengthen thy life, lessen thy meals."

[variously attributed to Benjamin Franklin, Poor Richard's Almanack, June 1733
and to Cicero (Roman orator 103-43 BC)]

Last updated 2002-01-05

The following table summarizes what I think are the most important interventions, in order of importance to health. Rating is my own assessment of the intervention, based on its importance and my confidence in the scientific backing to support it (1 = very important with strong evidence; 5 = may be helpful, with some evidence to support it). Note: underlined blue words are hyperlinks to Internet sites with supporting evidence; underlined red words are hyperlinks within this document to make navigation easier.

Please note, I collect these notes for myself, to keep references for various facts or speculations that are health-related. Some of these things are likely to prove useless or even harmful with time. Biggest changes since 2001-01:

1. Top emphasis on caloric restriction. This is clearly the most important thing to do! It reduces blood pressure, cholesterol, LDL (low-density lipoprotein, the form of cholesterol most associated with heart and blood vessel disease), and risk of diabetes to very low levels. It probably increases average life span by a large amount, though it will take a long time to find out.

2. I have modified my approach to fats. Omega-3 fats (fish, flax seed, etc.) are quite good for you! Avoiding animal fats (except fish oil) and certain vegetable fats (partially hydrogenated fats and most other sources such as corn oil that have far too much omega-6 fat) is still crucial. However carbohydrates and excessive sweet fruit are not good calorie source substitutes because they increase blood sugars, causing substantial long-term tissue damage. Instead, I now think it best to eat proportionally more calories from fish oil and certain vegetable fats (olive oil, nuts, flax seed, & avocados). In my own practice this means avoiding carbohydrates (bread, rice, sugar, potatoes, etc.), and eating more fish, nuts & some flax seed.

"He's gone off the deep end…"

Well, maybe so. However, a lot of nutrition medicine has been investigated recently, and some has been found to have merit. I think I should pass these findings on to those I know and love. See the end for more reasons for all of this.

I think it is most effective to reduce the likelihood of the things most likely to kill (heart disease, stroke, diabetes and cancer) or disable (aging, heart disease, stroke, hypertension, diabetes, arthritis, obesity, and mental/brain diseases). Certain specific habits, foods, dietary modifications, and supplements have been demonstrated to do these things.

So what? What if we could not just reduce but eradicate cancer, diabetes, heart disease, etc. – how much would be gained? It turns out that all this would NOT increase his life expectancy by more than a few years. The average person's longevity gain from the utter eradication of cancer from human experience would be 3.2 years of life. Elimination of ischemic heart disease would add 3.6 years. Elimination of these plus all circulatory diseases and diabetes would add a total of 15 years (Olshansky SJ, Carnes BA, Cassel C. In search of Methuselah: estimating the upper limits to human longevity. Science 1990 Nov 2; 250(4981):634-40). Thus aging catches up to us all even in the setting of elimination of the killer diseases – basically the body will wear out. On the other hand, there is strong evidence of a much greater increase in lifespan from caloric restriction, and there are hints that reduction of free radical damage, inflammation and glycation may add yet more useful, happy years.

Note that aging and our inevitable death are due to multiple factors. None of these can be eliminated; they can only be reduced in frequency or put off for a longer period of time. Any intervention that leads to better health or longer life applies on average; for any one person it may or may not happen to work. For example, a smoker may live to be 99 yrs old, while Jim Fix (the runner) died at about 49 yrs of age.

One interesting theory points out that aging and death are direct and inevitable consequences of systems redundancy: Gavrilov LA, Gavrilova NS. The Reliability Theory of Aging and Longevity. J Theor Biol 2001 Dec 21;213(4):527-545. http://www.src.uchicago.edu/~gavr1/JTB-01.pdf. PMID: 11742523

Reliability theory is a general theory about systems failure. It allows researchers to predict the age-related failure kinetics for a system of given architecture (reliability structure) and given reliability of its components. Reliability theory predicts that even those systems that are entirely composed of non-aging elements (with a constant failure rate) will nevertheless deteriorate (fail more often) with age, if these systems are redundant in irreplaceable elements. Aging, therefore, is a direct consequence of systems redundancy. Reliability theory also predicts the late-life mortality deceleration with subsequent leveling-off, as well as the late-life mortality plateaus, as an inevitable consequence of redundancy exhaustion at extreme old ages. The theory explains why mortality rates increase exponentially with age (the Gompertz law) in many species, by taking into account the initial flaws (defects) in newly formed systems. It also explains why organisms "prefer" to die according to the Gompertz law, while technical devices usually fail according to the Weibull (power) law. Theoretical conditions are specified when organisms die according to the Weibull law: organisms should be relatively free of initial flaws and defects. The theory makes it possible to find a general failure law applicable to all adult and extreme old ages, where the Gompertz and the Weibull laws are just special cases of this more general failure law. The theory explains why relative differences in mortality rates of compared populations (within a given species) vanish with age, and mortality convergence is observed due to the exhaustion of initial differences in redundancy levels. Overall, reliability theory has an amazing predictive and explanatory power with a few, very general and realistic assumptions. Therefore, reliability theory seems to be a promising approach for developing a comprehensive theory of aging and longevity integrating mathematical methods with specific biological knowledge. Copyright 2001 Academic Press.

To me this theory seems at least partially correct. Another way of thinking about it is that we get more frail with age. The theory implies that the approach to health should be multi-factorial. I think one should improve health in as many areas as possible (avoidance of toxins; reduction of specific diseases such as Alzheimer's & cardiovascular disease; safety; exercise; proper diet; caloric restriction; etc.)

What kind of science are these notes based on?

Much of it is science based on observations disease rates of various populations. For example,

1. The Japanese have a low level of prostate cancer and Alzheimer's disease, and a high level of stomach cancer. On the other hand, Second-generation Japanese-Americans have the same rates of these diseases that Americans in general have.

2. Doctors observed that people who took aspirin for very long periods (such as those with arthritis) had a much lower rate of heart attacks, while those who took or ibuprofen (Motrin) had lower rates of Alzheimer's disease and colon cancer.

3. Scientists were first alerted to the many benefits of the essential fatty acids (usually from fish) EPA and DHA in the early 1970s when Danish physicians observed that Greenland Eskimos had an exceptionally low incidence of heart disease and arthritis despite the fact that they consumed a high-fat diet. The so-called “Mediterranean diet” (olive oil, fish, etc.) was also observed to be associated with a low incidence of heart disease.

Once these observations were made, studies were done to figure out which factors caused the observed differences. Certain things were shown to correlate to these differences (for example, women with the highest folic acid intake were shown to have the smallest number of children with spina bifida, a cause of cerebral palsy). This correlation does not mean cause and effect. To get that you have to do carefully controlled, prospective studies. This last step takes a lot of time, money, and careful science, and has been done for only a few factors. Even then you cannot be certain there was not a confounding factor of which the scientists were unaware. Three contrasting examples:

1. Studies eventually proved that folic acid is indeed what prevents spina bifida, and that the recommended daily allowance of folic acid is insufficient. Other studies have since shown the high importance of folate for prevention of cardiovascular disease and colon cancer (75% reduction found in a study of multivitamin use in women, Annals of Internal Medicine, Vol. 129, No. 7) as well!

2. Decades ago it was observed that high cholesterol levels in the blood correlated with a high rate of heart disease. At first a lot of experts recommended cutting down on cholesterol intake in foods. Since then several forms of cholesterol in the blood have been identified, and it has been shown that high fat intake makes your cholesterol level go up much more than eating cholesterol itself.

3. Intensive research has discovered that two of the fish fats (oils) that Eskimos consume in large quantities, EPA and DHA, were actually highly beneficial. More recent research has established that EPA and DHA) play a crucial role in the prevention of atherosclerosis, heart attack, asthma, depression, and cancer (associated with a >50% reduction in breast cancer risk: Pala, Valeria, et al. Erythrocyte membrane fatty acids and subsequent breast cancer: a prospective Italian study. Journal of the National Cancer Institute, Vol. 93, July 18, 2001, pp. 1088-95). Clinical trials have shown that fish oil supplementation is effective in the treatment of many disorders including sudden cardiac death, high blood pressure, rheumatoid arthritis, diabetes, ulcerative colitis, and Raynaud's disease. Epidemiological data from Japan and elsewhere suggest other benefits as well, including a reduced risk of prostate cancer. And just recently, the Lyon Diet Heart Study, a randomized secondary prevention trial aimed at testing whether a Mediterranean-type (actually Crete) diet may reduce the rate of recurrence after a first myocardial infarction, found a striking reduction in risk of heart disease from this diet. Other studies (Arthritis Rheum 1995 Aug;38(8):1107-14 and American Journal of Clinical Nutrition, Vol. 71, No. 1, 349S-351s, January 2000) showed that fish oil was effective in treatment of rheumatoid arthritis.

1. Simopoulos, Artemis. Omega-3 fatty acids in health and disease and in growth and development. American Journal of Clinical Nutrition, Vol. 54, 1991, pp. 438-63

2. Pepping, Joseph. Omega-3 essential fatty acids. American Journal of Health-System Pharmacy, Vol. 56, April 15, 1999, pp. 719-24

3. Uauy-Dagach, Ricardo and Valenzuela, Alfonso. Marine oils: the health benefits of n-3 fatty acids. Nutrition Reviews, Vol. 54, November 1996, pp. S102-S108

4. Connor, William E. Importance of n-3 fatty acids in health and disease. American Journal of Clinical Nutrition, Vol. 71 (suppl), January 2000, pp. 171S-75S

5. DiGiacomo, Ralph A. , et al. Fish-oil Dietary Supplementation in Patients with Raynaud's Phenomenon: A Double-Blind, Controlled, Prospective Study. The American Journal of Medicine, Vol. 86, February 1989, pp. 158-164

Another example: women who have a healthy life style can reduce their risk of heart attack and stroke by 80%.

Things with good evidence, that I think most people should do now unless there is a contraindication (a reason not to).

1. Caloric restriction (CR). This is the only approach that has been proven to slow the aging process itself, as opposed to reducing the risk of premature death from specific causes such as heart disease! Of everything in these notes, this is the most important thing you can do. It is directly contrary to the US trend to eat more. According to the surveys conducted in 1977-1978 and 1994-1996, reported daily caloric intakes increased from 2239 to 2455 in men and from 1534 to 1646 in women. In 1932 Clive M. McKay of Cornell University discovered that reducing lab rats’ caloric intake while maintaining nutrition intake (protein & vitamins, etc.) radically prolonged their life span. Recent well-controlled studies show that reducing a lab rat's caloric intake by 50% increases its lifespan by 40%, cuts cancer rates in half, and allows it to retain brain function well beyond its ad-lib-fed (“eat what you want”) peers. It turns out that this reduction in aging applies to almost all animals studied, even to individual cells in a Petri dish. This includes reduction in the rates of cancer, endometriosis, and vascular disease, as well as increased life span and function. The science on this is very strong, with hundreds or perhaps thousands of supporting studies published in the peer-reviewed literature. Some examples from day-to-day life: small dogs live much longer than big dogs; small (both height and weight) people live longer than large people - this may be why women live longer than men. Lower caloric intake is associated with a lower rate of Alzheimer’s disease. Another example: studies have shown that all mammals, no matter what their lifespan, consume on average about 200 kcal per gram of tissue in one lifetime; thus there may be a trade-off between eating and life span.
   
   There has not yet been a complete human study: that could take 100 years to do. Instead we have to rely on:
   1) Shorter-lived animal studies, particularly those that are genetically close to human.
   2) The experience of Okinawans, who typically eat 10-40% less calories for a given body frame than Americans because of a cultural practice called “hara hachi bu”, or eating until 80% full.
   3) Evidence of the beneficial effects of CR in people based on markers of aging (diabetes, high blood pressure, etc.)
   In an on-going NIH-sponsored study of CR in monkeys, the markers of aging all point to the same thing happening in primates. This study has been going on since 1987, and has already demonstrated that CR completely prevents diabetes type II in these animals and increases their average life span. Whether CR also increases maximal life span will not be known for 10-15 yr.
   The following is data from the Okinawa Centenarian Study presented at the American Geriatrics Society annual meeting, 2001: "Compared with Americans, Okinawan elders
   * are 75% more likely to stay mentally sharp into old age
   * get 80% less breast and prostate cancers
   * get 50% less ovarian and colon cancers
   * have 50% fewer hip fractures
   * have 80% fewer heart attacks
   * have cholesterol levels comparable to Boston Marathoners"
   Of note is that Okinawans also eat different things than Americans (more fish and soy, for example). But they also live longer than their peers on the Japanese mainland, while eating much the same types of food.
   Some people have voluntarily calorie restricted for about 10 yr. to date; their risk factors are reduced substantially: blood pressure, cholesterol, LDL, and rate of diabetes by a greater degree than I personally have seen from any other intervention. In addition their markers of aging are slowed. Of all the things you can do, this is probably the most important, but should be combined with all of the things below. If you want more info, look it up on the web at the sites below, or read Walford’s books (He is a UCLA pathologist who has written extensively about CR. I have not read his books).
   
   If you simply look at a table of life expectancy vs. obesity it appears that there is a decrease for both excessive fat and excessive thinness. This has led to the false thought that it is harmful to be "too thin". In point of fact, the thin people included in these charts are often smokers or those with chronic disease. (Solomon CG, Manson JE. Obesity and mortality: a review of the epidemiologic data. Am J Clin Nutr 1997 Oct;66(4 Suppl):1044S-1050S.) Available epidemiology shows that mortality (among nonsmokers without preexisting medical conditions) is lowest in persons of BMI <19.

1. How does it work? Many ideas, all of which have been demonstrated to have basis in fact:
   Reduced risk of diabetes “91% of type 2 diabetes is attributable to lifestyle, primarily to being overweight” – see NEJM 2001-09
   Reduced high blood pressure and heart disease
   Reduced intake of harmful substances and carcinogens
   Reduced activity of your body's cells
   Reduced glucose-caused destruction of your body's proteins
   Reduced production of free radicals, toxins and “metabolic garbage” from normal metabolism (!)
   Reduced DNA damage (both mitochondrial and nuclear).

2. How much weight do you need to lose? Well, caloric restriction is eating less (calories!!) rather than being skinny that does it, but a weight goal is a convenient proxy for calorie counting. [Please note that some people will be naturally chubby while on CR, but - if mouse studies can be extended to humans - they will derive the same beneficial effect from CR that skinny people do.] If you look up the average weight for your sex, height, and frame, set a goal of 10-20% below that weight. For example, the average weight for a man of my 5' 9" height is about 150 lbs: my weight goal would be from 120-135 lbs. This weight loss should be done over a long period, perhaps 3 years (longer if you start out significantly overweight). Another way is to aim for a body mass index (BMI) of 18 to 20. Again, losing weight by increased physical activity is not the same as CR, and although it improves cardiovascular health it does not slow aging. Indeed, excess exercise may be harmful (high production of free radicals). When you reach the goal weight your body is not anorectic, but is similar to that of a slender pre-adolescent.

3. This is not a temporary diet, but a permanent change in how much you eat.

4. There appears to be a somewhat linear effect: the less you eat the better, up to a point.

5. There are some serious problems at very low calorie levels (corresponding to a weight 25% below average for age and sex or less). These problems include cold intolerance (but good heat tolerance), decreased libido in men, and the same problems that are found with anorexia nervosa. Childbearing or nursing women can remain relatively thin and still be healthy, but should not practice CR per se. Children also should not practice CR, but staying slender (BMI = 17) until adolescence is wise.

6. Caloric restriction should be started in adolescence if possible. The beneficial effects of CR are reduced when it is started in middle age - your body has already been exposed to the causes of aging - but it is still worthwhile.

7. If you eat less you must ensure that your nutrition is adequate. Get enough protein, essential fats, berries & vegetables, vitamins and minerals (especially calcium, but avoid iron). If you lose a lot of weight and simultaneously cut down on protein and calcium you may be at risk for bone weakness from osteoporosis.

Relevant web sites:

FAQ

Research http://o112.ryd.student.liu.se/calorie_restriction/

http://henson1.ssu.edu/~agdigiov/Topics/CR_nt.htm

Benefits http://www.the-scientist.com/yr1997/may/research_970526.html

http://whyfiles.org/057aging/lo_cal.html

http://www.sciencedaily.com/releases/2001/01/010123075904.htm

http://www.sciencenews.org/20001125/fob3.asp

http://www.liv.ac.uk/~adelam/biolage.htm

http://www.healthy.net/asp/templates/article.asp?PageType=Article&ID=221

http://www.lougehrigsdisease.net/als_news/990112caloric_restriction_reduces_risk.htm

http://walford.com/index.html

http://www.infoaging.org/b-cal-6role.html

http://clos.net/calorie_restriction_refs.htm

http://www.washingtonpost.com/wp-dyn/articles/A6432-2001Jul16.html

http://www.sciam.com/specialissues/0600aging/0600taubes.html

http://www.stn2.com/articles/view.php3?language=english&type=article&article_id=218391731

http://www.benbest.com/calories/cran98.html

Side effects
An interesting USDA analysis of varied types of diets

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The Independent - London (edited by skm)
Lewis Wolpert

February 09, 2001

NOW THAT the Christmas and New Year celebrations are a distant memory, it is probably a good time to think about how food makes us age. Like it or not, the evidence from animals is that limiting food intake can significantly extend the life span of a variety of animals.

When rats are kept in the laboratory under pleasant conditions but with an intake of food such that after weaning they get 50 per cent less than their well-fed neighbors, they live about 40 per cent longer. The oldest rat with high-food intake is around 1,000 days, but there are those on the restricted intake who get to 1,500 days.

Vitamins and minerals must be included in the diet, but it does not matter if the reduced calories come from carbohydrates, proteins or fat. Low intake of calories suppresses most of the diseases so common in older animals such as cancer, high blood pressure and deterioration of the brain. In female rats, the age at which the ability to reproduce is lost is extended from 18 months to 30 months. If the feeding-regime is returned to full feeding, the aging process seems actually to be accelerated.

Why can the underfed rodents live so long? The key lies with oxygen and free radicals. Oxygen is required in the cells to produce energy from the molecules derived from the food. This production of energy is fundamental to life, and takes place in small structures in the cell called mitochondria. Free radicals, which are highly reactive molecules, are a natural product of this process; they can damage the mitochondria and this leads to less energy production, which is a characteristic of aging. This damage to the mitochondria leads to the release of more free radicals, so setting up a positive-feedback loop that makes things worse and worse.

There is some evidence that we humans could also delay aging by reducing our calorie intake. On the Japanese island of Okinawa, there are significantly more centenarians than on other Japanese islands. The death rates from stroke, heart disease and cancer are only about two thirds of that for Japan as a whole and the death rate for 60- year-olds is half the national average. It is unlikely to be just a coincidence that the average adult food-intake was, for cultural reasons, 20 per cent less than the Japanese average, and that the school children eat less than two thirds of that recommended for Japan.

Lewis Wolpert is professor of biology as applied to medicine at University College London

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See slide 55 on lab mouse (?) lifespan from Extro 3 Conference in San Jose, California (August 1997)

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Another reference, from the “Biosphere 2” experiment on people done in a two-year study near Tucson, Arizona:

Walford RL, Harris SB, Gunion MW. [The Biosphere 2 diet], low in calories (average, 1780 kcal/day), low in fat (10% of calories), and nutrient-dense, conforms to that which in numerous animal experiments has promoted health, retarded aging, and extended maximum life span.

We report here medical data on the eight subjects, comparing preclosure data with data through 6 months of closure. Significant changes included:

(i) weight, 74 to 62 kg (men) and 61 to 54 kg (women);
(ii) mean systolic/diastolic blood pressure (eight subjects), 109/74 to 89/58 mmHg;
(iii) total serum cholesterol, from 191 +/- 11 to 123 +/- 9 mg/dl (mean +/- SD; 36% mean reduction), and high density lipoprotein, from 62 +/- 8 to 38 +/- 5 (risk ratio unchanged);
(iv) triglyceride, 139 to 96 mg/dl (men) and 78 to 114 mg/dl (women);
(v) fasting glucose, 92 to 74 mg/dl;
(vi) leukocyte count, 6.7 to 4.7 x 10(9) cells per liter.
We conclude that drastic reductions in cholesterol and blood pressure may be instituted in normal individuals in Western countries by application of a carefully chosen diet and that a low-calorie nutrient-dense regime shows physiologic features in humans similar to those in other animal species.

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One quite reasonable theory as to why caloric restriction is effective in reducing aging is the MARS theory. It may also apply to possible beneficial effects of certain antioxidants, though this is less clear.

MARS (mitochondria, aberrant proteins, radicals, and scavengers) theory is an integrative model or network theory of aging. It's a quantitative systems approach presented by Kirkwood and Kowald (1994,1996).

...They developed the idea that aging and longevity may be understood as the outcome of a network of maintenance processes that control the capability of the system to preserve homeostasis. What is important about their analysis is that it is a quantitative model....(they) considered that the free-radical theory and the protein error theory were each important but incomplete descriptions of the aging processes within a cell--incomplete because each could well interact with one another at particular points and provide sources of damage and/or protection not specifically predicted by either theory alone. As one example of such interaction Kowald and Kirkwood suggested that free radicals could damage enzymes and thereby provide another source of abnormal protein not specifically foreseen the original theory. To the extent that such abnormal proteins included abnormal antioxidant enzymes, the level of protection against free radicals would be reduced because of this protein error another source of damage not specifically foreseen by the original theory.
...Other sorts of interactions comprising these two theories of aging could be composed of free radicals, antioxidant-enzymes, antioxidant scavengers, and the ribosomes, synthetases and/or mRNA's involved in protein synthesis...In this model, the free radical production rate is the key variable and depends on the kinetics of their production in the free radical source (mitochondria). and their destruction in their sink (superoxide dismutase and other antioxidants). The production of free radicals thus depends on the level of energy provided by the mitochondria, and on the synthesis, turnover, and degradation of the mitochondria themselves.. The model also takes into account the diffusion of free radicals out from the mitochondria into the cytoplasm and the damaging effects such radicals might have on different classes of cytoplasmic components. (they) derived a series of 15 differential equations to describe the interactions of the systems components. Subsequent computer simulations yielded some interesting results. High levels of free radicals, insufficient levels of free-radical protection, and high levels of protein error each lead to an integrated breakdown of homeostatic process and cell death. This particular simulation suggests that the main targets of free-radical damage in the "typical" cell are the mitochondria, damage to which results in decreased energy production, an increased damage rate to various cytosolic proteins, and a shift in the proportion of damaged or erroneous proteins present in the cell. The net result of these insults is the breakdown homeostasis. In effect the stability of the cell is undermined by the instability of one of the major components (mitochondria) that initiates an eventually disastrous positive feedback cycle of free-radical production and ensuing damage to mitochondria and proteins. The model is obviously an incomplete description of the real cell, as its authors are the first to acknowledge. Yet the fact that the model yields a predicted lifespan that is approximately correct is reassuring.... Given this simulation "virtual immortality" might be achieved if 55 percent of the total energy of the simulated cell were devoted to repair and/or prevention of free radical and oxidative damage. Below that level of expenditure, the loss of cellular homeostasis was inevitable although it could be significantly modulated by various treatments.
The Biology of Aging, Arking, 1998

The theory and computer simulation provide an underlying theoretical rationale for a combined approach for using CR and/or a number of segmental interventions the sum of which may provide greater benefits in terms of longevity.

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High Body Fatness, not Low Body Muscularity Predicts Disability in Elderly

Although one would have thought that low muscularity would be the source of most of the mobility problems of the elderly, a new study¹ reports that it is high body fatness, not low fat-free mass that predicts such problems.

The scientists used data from the Cardiovascular Health Study to study the problem. They examined body composition and self-reported, mobility related disability in 2714 women and 2095 men aged 65 to 100 years. The odds ratio for disability in the highest quintile of fat mass was 3.04 for women and 2.77 for men compared with those in the lowest quintile. Low fat-free mass was not associated with a higher prevalence of disability. Age, physical activity, chronic disease, or other potential cofounders did not explain the increased risk of disability.

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Obesity is Mortality Risk Factor in the Elderly, Too

Another study² reports that, contrary to an earlier study that appeared to indicate that obesity is not as risky in older as in younger individuals, obesity increased mortality in both old and young individuals. However, due to the increasing impact of age on mortality, the relative risk of obesity as a mortality risk factor is lower in older than in younger persons. For example, during the 11-year follow up, 1.5% of reference weight young men (30-39 at the start of the study) died, whereas 3.6% of obese men in the same age group died. In the reference weight group of older men (60-69 at start of the study), 25.3% died in the follow-up period, while 31.9% of the obese men in the same age group died. Hence, the relative mortality risk of obesity is higher in younger than in older men, but the mortality risk differences between obese and reference weight groups was higher in the older than the younger men. The overall finding was that the BMI (weight in kilograms divided by (height in meters)²) associated with the lowest mortality was 18.5-24.9 in individuals 30-74 years old.

No matter how you look at it, excess body fat is a health risk, especially if you would like to live a very long time.

¹ Visser et al, "High Body Fatness, But Not Low Fat-free Mass, Predicts Disability in Older Men and Women: the Cardiovascular Health Study," Am. J. Clin. Nutr. 68:584-90 (1998)

² Stevens, "Impact of Age on Associations Between Weight and Mortality," Nutrition Reviews 58(5):129-137 (2000)

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Field AE, Coakley EH, Must A, et al. Impact of Overweight on the Risk of Developing Common Chronic Diseases During a 10-Year Period. Arch Intern Med. 2001;161:1581-1586

Background Overweight adults are at an increased risk of developing numerous chronic diseases.

Methods Ten-year follow-up (1986-1996) of middle-aged women in the Nurses' Health Study and men in the Health Professionals Follow-up Study to assess the health risks associated with overweight.

Results The risk of developing diabetes, gallstones, hypertension, heart disease, and stroke increased with severity of overweight among both women and men. Compared with their same-sex peers with a body mass index (BMI) (calculated as weight in kilograms divided by the square of height in meters) between 18.5 and 24.9, those with BMI of 35.0 or more were approximately 20 times more likely to develop diabetes (relative risk [RR], 17.0; 95% confidence interval [CI], 14.2-20.5 for women; RR, 23.4; 95% CI, 19.4-33.2 for men). Women who were overweight but not obese (ie, BMI between 25.0 and 29.9) were also significantly more likely than their leaner peers to develop gallstones (RR, 1.9), hypertension (RR, 1.7), high cholesterol level (RR, 1.1), and heart disease (RR, 1.4). The results were similar in men.

Conclusions During 10 years of follow-up, the incidence of diabetes, gallstones, hypertension, heart disease, colon cancer, and stroke (men only) increased with degree of overweight in both men and women. Adults who were overweight but not obese (ie, 25.0 BMI 29.9) were at significantly increased risk of developing numerous health conditions. Moreover, the dose-response relationship between BMI and the risk of developing chronic diseases was evident even among adults in the upper half of the healthy weight range (ie, BMI of 22.0-24.9), suggesting that adults should try to maintain a BMI between 18.5 and 21.9 to minimize their risk of disease. (my emphasis – SKM)

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2. Aging is inevitable and has many causes, including genetics and the slow cross-linking of proteins in your body. Two reducible factors have been shown to cause "aging" of cells and tissues. I think it is worth taking measures to reduce these factors. Actually, the most effective way to do both is probably caloric restriction.

   1. Direct, non-enzymatic glycation. This damage to your body tissue from sugars is what makes diabetics age so quickly. A recent English study suggests that even small elevations in blood sugar level (as measured via HbA1c) have a large effect on the risk for heart attack. Glycation is simply the direct chemical reaction between fructose or glucose in your blood stream (from sugar, starches, fruits etc.) and your body's proteins. In college chemistry you may have heard of this as the Maillard reaction. This reaction results in the proteins being degraded and losing their function: tissues become stiff, arteries hard, lenses opaque, spots form on your skin. This reaction is directly related to the fructose and glucose concentration in the blood, which is a complex interaction between what and when you eat, your body weight and body fat, your activity level, your body's insulin response, etc. This is too complex for me to sort out completely, but two things are clear (for non-diabetics): insulin responsiveness declines in obese people, and glucose level rises fast after eating a lot of simple sugars (a soda, fruit juice, ice cream, etc.) Therefore, simply keep slender and avoid large quantities of sweets, just like your mother told you. Another approach is to get less of your calories from carbohydrates and more from fats: but if you do so, avoid animal fat, partially hydrogenated oils and omega-6 fats! A third approach is to eat many small meals each day instead of one or two large meals, to keep the peak glucose load down.
      Note also that glycation also occurs in the intestines and outside the body, and that the glycated proteins are readily absorbed. Thus it is probably best to not marinate meat in sugary liquids. I like plain soy sauce my self.
      One term used in discussing glycation is “glycemic index”, or the much more useful measurement of “glycemic load”. This refers to how much your blood glucose level rises after eating various foods. The glycemic load for sugar, rice, and bread would be very high; for asparagus and peanuts very low. If you want to minimize the glycation of your body’s tissues, practice caloric restriction and eat foods with low glycemic loads (not too much starch).
      The major sources of fructose in our diet are table sugar (half fructose!), fruit, honey, and high-fructose corn syrup that is a part of so many prepared foods at the grocery store, such as soft drinks, jams, & yogurt. It is probably worth avoiding too much of the sweet fruits, although berries (blueberries, raspberries, strawberries, etc.) have much less fructose and glucose, and seem to be fine. In addition, in the small study that showed increased triglycerides from fructose (1: Lingelbach LB, McDonald RB. Description of the long-term lipogenic effects of dietary carbohydrates in male Fischer 344 rats. J Nutr. 2000 Dec;130(12):3077-84.), there was a small increase in life span of fructose-fed animals.
      Some other foods with high glycemic index or load include: all starches, potatoes, bread, rice, sugar, honey, and breakfast cereals (except all-bran cereals); sweet fruits also have a high glycemic load but have the benefit of nutrients. This web site has an extensive glycemic index list.
      Some foods with low glycemic load include: onions, mushrooms, yams and whole grain or 100% rye bread (pumpernickel are all good), but mostly lots more vegetable 'fruits', i.e. peppers, tomato, cucumber, squash, eggplant; cruciferous vegetables (cabbage, broccoli, cauliflower, Brussels sprouts); and leafy green vegetables of all kinds.
      For a web site with an interesting (and I think fairly good, though vegetarian) food pyramid, see http://www.health.harvard.edu/newsletters/giload.shtml.

   2. Free radicals. These are intermediate chemical reactants, a by-product of living! They are very reactive and cause slow, continuous damage to cells and tissues all over the body, and may account for part of the aging process in the brain (Mechanisms of Aging and Development, 2000, Vol 116, Iss 2-3, pp 141-153.) As we age, free radicals are produced in greater amounts. The body has several systems to neutralize these reactive chemicals, and mutant lab animals with defects in these systems age and die rapidly. Fortunately there are a few things you can do to reduce the effect of free radicals. First, you can reduce the production of free radicals by eating less (see the section on caloric restriction). This is by far the cheapest and most effective (in theory) approach, with the fewest side effects! Second, you can get sources of "antioxidants", such as vitamin E, vegetables (especially spinach, broccoli and related vegetables) and fruits (especially blueberries, strawberries, raspberries [shown to reduce risk of cancer in the lab], prunes and purple grape juice), green tea, and other things such as coenzyme q10. Antioxidant-rich blueberries, spinach and strawberries have been shown to improve brain function in rats.
      
      In a study of death rates related to diet and other factors (from Epidemiology 1997 Mar;8(2):168 74): the mortality hazard ratios with ... increasing [amounts of]... nuts (1.00, 0.60, 0.56), fruits (1.00, 0.38, 0.57), and green salads (1.00, 0.54, 0.65). Thus the often heard exhortation to eat more fruits & vegetables. All of these foods have antioxidants of various kinds.
      
      Coenzyme q10 is particularly intriguing as one of the few antioxidants that have effect in the brain and mitochondria (Matthews RT et al. Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects. 1998. Proc Natl Acad Sci USA 95: 8892-8897) and may protect against stroke damage and degenerative brain disorders.
      
      Here is a useful summary using the antioxidant analysis called ORAC. The “best” antioxidant foods are the ones on top of the list, with the most effect (in the test tube) per calorie. In vivo, spinach comes out on top of several tested (see the USDA article Cans Foods Forestall Aging?), but there are many different types of anti-oxidants, and it may be best to eat a variety of them every day. The list below is of many but not by any means all anti-oxidant food sources. The ORAC/Cal is what counts most – the most “bang for the buck”:

Food ORAC/ ORAC/

Cal g

----------------------------------------

Spinach 59.9 13

Strawberries 51.7 15.5

Blueberries 40.2 22.5

Blackberries 39.4 20.5

Kale 36 18

Alfalfa sprouts 32.8 9.5

Broccoli flowerets 32.1 9

Red pepper 28.9 7.5

Brussels sprouts 22.8 9.8

Beets 20.7 8.9

Orange 17 8

Pink grapefruit 16.3 4.9

Cauliflower 15.6 3.9

Eggplant 15 3.9

Cherry 14 7

Cabbage 14 3.5

Garlic 13.1 19.5

Onion 11.8 4.5

Red grape 11.1 7.9

Kiwi 10.7 6.5

Cantaloupe 8.6 3

White grape 6.7 4.5

Apricot 4.2 2

Sweet potato (yams) 3 3.5

Corn 1.1 4

In other reports, prunes come out on top in antioxidants per gram but not per calorie. There are different assays for antioxidant activities; among other highly effective antioxidant sources are tea (green & black) and garlic. I think it is wise in this as in other things to eat a variety of foods that are good for you.

Remarkably, some essential oils (spice oils) have far more antioxidant power on ORAC assays than fruits and vegetables. (n. b., I think the data quoted at this site are correct, but the hype is beyond reason, so beware!) Cloves come out on top, with two drops of oil equivalent to 2.5 cups of blueberries. However, clove oil (eugenol) may be toxic, and is used as a local anesthetic by dentists. I do not think it wise to use it as a supplement, though ground cloves are tasty in some foods.

3. Which fats you eat is VERY important. Please be aware however that this is a moving target: the recommendations are confusing and change dramatically with time as understanding grows and new studies are done.
   
   In summary:
   Eliminate partially hydrogenated fats
   Reduce omega-6 fats
   Get enough omega-3 fats
   (I am unsure of saturated fats – some good points and some bad?)
   Perhaps the total healthy fat intake could account for 30-50% of calories
   
   Definitely important: try to eliminate partially hydrogenated vegetable oils (very hard to do, as these make up margarine and are the major fat used in most prepared foods such as cookies, cake mixes, Raman noodles, bread, snacks, margarine, etc.: see Margarine, Fatty Acids and Your Health). Hydrogenation makes oils solid, but partially hydrogenated oils have trans-fats that are a NON-FOOD: they are not easily metabolized in the body and accumulate over time, increasing your risk for heart attack. They may also increase the risk of adult-onset diabetes (Dietary fat intake and risk of type 2 diabetes in women. American Journal of Clinical Nutrition, Vol. 73, No. 6, 1019-1026, June 2001.)
   
   Cut down on animal fat (except fish), long-chain saturated fats, and certain types of vegetable fats such as corn oil (see Essential fatty acids in health and chronic disease.) This will help reduce the incidence of stroke, heart attack, and cancer.
   
   Medium and short-chain saturated fatty acids may be a good source of calories. They do not raise blood triglyceride levels very much. As opposed to long-chain sources (animal fat etc.) they tend not to cause accumulation of body fat. Some of the best sources of this are coconut oil and palm kernel oil, despite the brief but well-publicized warning of several years ago about tropical oils (the possibly mistaken warning was based on the high levels of saturated fats in these oils, but this is controversial). Because these fats are saturated they cannot be oxidized into plaque-forming fats: they do not become rancid.
   
   Oils that can become rancid are can be oxidized: these oils are potentially toxic to mitochondria, cause atherosclerotic plaque formation, and should generally be limited (but not eliminated – this group includes the essential fatty acids) in the diet. These oils are the unsaturated fats, of which polyunsaturated fats may be the worst.
   
   The amount of good fat in your diet should perhaps be about 30 or 40% of your total calories. Modification of fat intake is far more important than how much cholesterol you eat. What is good fat? Moderate quantities of mono-unsaturated fats are good, especially those found in olive oil, avocados, canola oil, and nuts (pecans, walnuts, hazelnuts, almonds, pistachio & macadamia nuts at least). Problem with unsaturated fats: they are easily oxidized by free radicals, and the oxidized fatty acids are one of the primary causes of atherosclerotic plaque formation.
   
   Epidemiological studies show that the countries that have the highest fat diet, such as the USA, UK and Canada, have the highest incidence of Alzheimer’s disease, while the countries with the lowest intake of fat (i.e., Japan, Nigeria and China) have the lowest incidence. Of note is that this relationship is correlated with average body weight, and if that were taken into account, proportional fat intake might drop out as a risk factor. My guess is that it is best to have a “normal” (30 to 40% of calories) intake of fat, but keep the total down by caloric restriction (again this comes up!)
   
   Omega 3 fats in moderation are probably particularly important, as summarized in a review article. Fat in fatty fish has a large amount of omega 3 and is probably good (e.g., salmon). It even turns out that at least in mice fish fat does not induce nearly as much weight gain or hyperglycemia as does lard, soybean oil, or safflower oil. On the other hand, an older study from 1995 found no protection from heart attacks by fish intake.
   
   The current Western diet is too rich in omega-6 fat from various vegetable sources, and this is thought to cause much disease. Current theory (see the National Institutes of Health site discussing eicosanoids) is that the ratio of omega-3 to omega-6 fat should be about 1 to 1; the average Western diet has a ratio of about 1 to 15! In order to get some balance, eat some source of omega-3 fat. I know of a few sources: small, fatty, cold-water fish (such as salmon, herring, cod and sardines), walnuts, canola oil, and flax seed; there are probably several others. Corn, sunflower, safflower, soy and cottonseed oils have lots of omega-6 fat – actually many nuts do too. Studies show that omega-3 oil helps to prevent heart attacks and probably helps prevent depression or reduce bipolar psychosis. A large, multi-center, case-controlled study in the 2001-08 journal Archives of Ophthalmology showed that fish oil reduces the rate of macula degeneration (while the omega-6 fat linoleic acid raises the risk).
   
   In addition, the type of omega-3 oil is important (EPA, DHA, and alpha-linolenic acid (ALA) – see this description of the essential fatty acids and deficiency symptoms). EPA and DHA are long-chain omega-3 fats from fish, which in turn get it from eating cold-water marine sources. Most fresh fish in the store is farm-raised fish, and some may have less EPA and DHA if they are fed on corn or the like.
   
   For psychological health it may be that the more EPA the better, and the more DHA the worse (the reverse may be true for nursing or pregnant women, as DHA appears to be important for brain development). If you have problems with depression, the best way of getting this ratio of omega-3 oil may be to take a supplement such as OmegaBrite (EPA to DHA ratio of 7:1), Omega-3s "700" (The Solgar Vitamin Company), Pro-Omega from the company Nordic Naturals, GNC's Fish Body Oils 1000 (30 percent concentrated omega-3 fatty acids, with an EPA to DHA ratio of 1.5:1). For other health concerns, plain fatty fish is just fine!
   
   ALA is from flax seed (highest concentration) and certain other plant sources such as canola. ALA has been shown to reduce cardiac death. Flax oil has the potential problem of associated increased rates of prostate cancer in four epidemiological studies. However, flax seed per se (as opposed to flax oil) has additional benefits of lignans and fiber that may make using freshly ground flax seed helpful overall in a healthy diet, particularly for women. In addition the studies showing problems were not controlled for proper use of the flax. Neither flax nor canola oil should be used for frying (use olive oil, coconut oil, or butter), nor should flax oil or anything other than freshly ground forms be used. Otherwise the risks may be increased due to oxidation of the oil. In addition, a study showed that the benefit of the Mediterranean Diet (rich in olive oil and fish) is at least in part from mono-unsaturated fatty acids (MUFA) or ALA. So getting the shorter chain omega-3 fats from vegetable sources probably does help, and the longer chain omega-3 fats from fish help even more.
   
   The NIH has a table of omega-3 vs. omega-6 fatty acids, listed as short or long, 6 or 3.

Omega6 Fatty Acids

------------------

Linoleic Acid (LA) ................. C18:2n6

Gamma Linolenic Acid (GLA) .......... C18:3n6

Dihomogamma linolenic Acid (DGLA).... C20:3n6

Arachidonic Acid (AA) ............... C20:4n6

Omega 3 Fatty Acids

-------------------

Alpha Linolenic Acid (ALA), (LNA) ... C18:3n3

Eicosapentaenoic Acid(EPA) .......... C20:5n3

Docosahexaenoic Acid (DHA) .......... C22:6n3

Contraindications: None.
Potential problems: Too much fish (of most types) is not good for children or potentially pregnant women because of tiny amounts of mercury in fish. Avoid bottom-dwelling fish, fresh-water fish, bluefin (vs. albacore) tuna, mackerel and shark: the latter three are large fish that live long enough to accumulate quantities of mercury and are thus potentially dangerous if you eat them frequently. The Environmental Working Group says there are some fish considered safe for pregnant women, including farm-raised trout and catfish, shrimp, fish sticks, flounder (summer), wild pacific salmon, croaker, mid-Atlantic blue crab and haddock.

4. Take low-dose, non-buffered (the buffer has aluminum) aspirin, perhaps ¼ tablet every other day. This does two things:

   1. Reduces your risk for heart attacks (the #1 killer!) by 40%.

   2. May reduce your risk for colon cancer (the #2 cancer killer after lung cancer - and you can avoid this by not smoking) by 40%.

   3. May reduce the overall risk for strokes (although it increases the risk of a hemorrhagic stroke).

Be sure to wait about 2 hours after taking low-dose aspirin before taking ibuprofen (Motrin): ibuprofen seems to block the blood-thinning properties of aspirin.

Contraindications: stomach upset or gastritis with aspirin, bleeding problems.
Potential problems: stroke, bleeding problems, stomach upset, gastrointestinal bleed (can be very serious or deadly!), and if you have kidney problems it may cause an increased rate of kidney failure.

5. Reduce the homocysteine level in your blood by taking about 1 mg (1000 mcg) of folate (folic acid) each day. No, your normal diet does NOT have enough folate, even if you eat vegetables and fruit. The Recommended Daily Allowance (RDA) is 400 mcg and is too little. Common multivitamins have 400 mcg of folate. Folate works in coordination with vitamins B6 and B12 to reduce the homocysteine level in your blood. In fact, folate should be taken with B12 to prevent nerve damage if you happen to have B12 deficiency (rare in youth). Folate definitely does the following:

   1. Reduces the risk for heart attack and other blood vessel disease.

   2. Greatly reduces the risk for spina bifida if taken during early pregnancy

In addition, folate probably also reduces your risk for strokes, certain cancers (colon and breast), and depression.
Coffee prepared in the European fashion (very thick and muddy) may increase homocysteine levels, although only decaffeinated coffee has been shown to be associated with a higher rate of heart attack (increased by 25% when compared to non-drinkers; Am J Epidemiol 1999 Jan 15;149(2):162-7.)

Contraindications: None.
Potential problems: None.

6. Get out of the sun, and use maximum sun block (SPF 45 to 50) if you have to be out in the sun. A sign in the Dermatology Clinic at my hospital says "Wear sun block all day, every day." A suntan is not enough to protect you. Besides causing the very common skin cancer, sunlight (along with smoking) is probably responsible for 80% of the premature skin aging changes. If you wonder if it really makes a difference, just look at the top and bottom of your forearm. The top was exposed to the sun a lot: if you are like me it is covered with spots, wrinkles, and blemishes. The bottom is relatively protected and is child-like. The best protection is to avoid exposure by wearing clothes and a hat; UV-protecting sunglasses or polycarbonate glasses will protect your eyes and eyelids.

Contraindications: None.
Potential problems: Sunlight helps your body make the active form of vitamin D: just make sure you get enough vitamin D in your diet.

7. Drink tea, preferably green tea. Repeated studies show this reduces the risk for cancer. The caffeine in tea and coffee may also help reduce the risk of Parkinson's disease. I have seen it suggested that one drink four cups of green tea each day, and I think this is correct. Apparently the tea should be steeped for at least three minutes to get the antioxidants into solution. Regular tea has less of the antioxidants but is still good; iced-tea mixes have much less.
   Contraindications: None.
   Potential problems: Caffeine and liquids also give a very small, temporary rise in blood pressure. If you want less caffeine, "rinse" the tea bag first for a few seconds with hot water: caffeine dissolves more easily than the antioxidants, so most of it is washed away. Also, to my mind green tea tastes bad. I add sweetener and spiced tea to make it palatable. Another problem with tea is oxalic acid that is present in tea just as it is in spinach. Calcium from milk either in the tea or just before or after should prevent its absorption.

8. Avoid charring or browning meat: this induces the formation of "heterocyclic amines" (heterocyclic amines are carcinogens, e.g. they cause cancer) and advanced glycosylation end-products (AGEs). Instead boil or microwave it and reduce how much you eat. This is probably most important for red meat (mammals including beef and pork); the risk may be lower for white meat (fowl & fish). A study from the University of South Carolina (reported in Journal of the National Cancer Institute 1998-11-18) found a five-fold increase in breast cancer rates in women who consistently ate well-done red meat. In addition, roasted nuts, cereal, etc. have AGEs; probably it is best to eat these with as little cooking and at as low temperatures as reasonable.
   Contraindications: None.
   Potential problems: Meat does not taste quite as good.

9. Cooking any protein with sugar or any thing with sugars in it (Bar-B-Q sauce, fruit, etc.) will also cause formation of substantial amounts of advanced glycosylation end-products (AGEs). 10% of these dietary AGEs are absorbed from the gut, and only 30% excreted. The rest may be deposited around the body and cause an eventual toxic buildup, as occurs in diabetics. The known or hypothesized toxic effects of these AGEs are primarily vascular. Evidence for this being a real problem that accumulates over time is found in studies of the new drug currently called ALT-711. This drug breaks up the cross-links of AGEs, presumably including those formed by high blood glucose levels and those of ingested AGEs. It has been shown to actually reverse the stiffening of the blood vessels that comes with age, and gives a beneficial effect on blood pressure. Clinical trials on this drug are still on-going.
   Note that AGEs are in nearly all food we eat – another reason to be on caloric restriction!
   
   

Contraindications: None.
Potential problems: Meat does not taste quite as good.

10. Colon cancer may be caused in part by red meat (doubles risk) and cured meats (including bacon, cured ham, salami, corned beef and pastrami). These meats cause the formation of carcinogenic N-nitroso compounds by bacteria in the feces, and may thus be a risk factor in colon cancer. Dairy products and soy do not (but soy may cause problems on estrogen-sensitive tissues and the thyroid). It is probably best to avoid eating large quantities of these meats. In addition, colon cancer risk may be reduced by 40% by eating a high-fiber diet. Another factor (perhaps the major one) associated with colon cancer is high body mass index (fatness). Factors that may decrease the risk: legumes (beans, soy, etc.), NSAIDs, and folate.

11. Avoid processed, cured and smoked meats such as hot dogs, bacon, smoked foods and lunchmeats: nitrites and the smoke processing seem to be the cause of much of stomach cancer. Smoked meats may be the cause of the very high stomach cancer rates in Japan and Italy. Simultaneous vitamin C & E intake may provide some protective effect against the carcinogenic properties of nitrites, by helping prevent formation in the gut.

See: Knekt P, Jarvinen R, Dich J, Hakulinen T. “Risk of colorectal and other gastro-intestinal cancers after exposure to nitrate, nitrite and N-nitroso compounds: a follow-up study.” Int J Cancer 1999 Mar 15;80(6):852-6. National Public Health Institute, Helsinki, Finland

Of various sources of N-nitroso compounds, intake of smoked and salted fish was significantly (RR = 2.58, 95% CI 1.21-5.51) and intake of cured meat was non-significantly (RR = 1.84, 95% CI 0.98-3.47) associated with risk of colorectal cancer. No similar association was observed for intake of other fish or other meat.

Contraindications: None.
Potential problems: None.

12. Spinach is good for you and rhubarb is good tasting, but they are full of oxalic acid, a substance that causes kidney stones. No fun if you get them! Fortunately, you can prevent the absorption of the oxalic acid in your intestines by drinking milk (or taking some other source of calcium) at the same meal you eat these foods.
    Contraindications: None.
    Potential problems: None.

13. Eat lots of vegetables and some fruit, especially tomatoes, broccoli (broccoli sprouts are best, and also other vegetables in the cabbage family have the same protective effects), purple grape juice, and berries (at least 1 cup and preferably 2 cups each day of blueberries, raspberries, and/or strawberries). These seem to help prevent cancer and stroke. Tomatoes in particular may need to be cooked and served with oil (such as pizza or spaghetti sauce) in order to help with the absorption of the active substance, lycopene. Broccoli sprouts in particular have been found to have especially high concentrations of glucoraphanins (10-50 times more than mature flowerets), and have been shown to prevent and slow the growth of breast cancer in rats. To get sufficient protective quantities of glucoraphanins from mature broccoli flowerets would require approximately 20% of your food to be from broccoli alone.
    Contraindications: None.
    Potential problems: Gas. Try cooking the vegetables more or eating different types and amounts.

14. Exercise regularly and moderately (30 minutes each day). This has repeatedly been shown to have several beneficial long-term health effects, including preservation of mental function and bone strength. Note that over-exertion may be harmful, both directly on the joints, and if you have to eat a lot to make up for calories used in exercise this partially defeats caloric restriction principles. Exercise helps keep your bones strong, helping to prevent osteoporosis-related fractures.
    Contraindications: Ask your doctor first before starting an exercise program!
    Potential problems: The increased metabolism of exercise causes some free radical induced damage and DNA damage – this can be partially prevented by using vitamin E. Exercise does NOT seem to affect life span (Epidemiology 1997 Mar;8(2):168 74)! Instead, I think of it as a way to improve the life I have.

15. Floss your teeth every day, in addition to brushing after every meal. This reduces your risk for heart attack and stroke, probably by reducing the chronic, low-grade gum infections.
    Contraindications: None.
    Potential problems: None.

16. Get your vaccinations! Influenza and pneumonia kill lots of people, especially after age 65 yr.

17. Most supplements (except vitamins A, E, & B12) should be taken in small doses several times each day instead of once a day. Just like medications they are not stored in the body, lasting about 4 hours, and thus may be best if taken three or four times per day. In my opinion, this includes folate, red grapes (grape juice or grape seed extract), tea, broccoli, and aspirin. An easy way to do this is to eat good food at every meal and take supplements with each meal and at bedtime. You should probably not take any supplemental vitamin A if you can avoid it: too much is quite toxic, and most people get plenty in the vegetables they eat.

18. Treat any infections. Chronic sinusitis and gingivitis (bad oral health) have been shown to predispose to heart disease!
    Recently the bacterium that causes stomach ulcers, Heliobacter pylori, has been strongly associated with stomach cancer (see NEJM 2001-09). They estimated that if this infection can be identified and treated with antibiotics we could eliminate the #10 cause of cancer death in America. Approximately 35% of Americans have H. pylori infection and do not know it: this appears to be associated with a 2.9% risk of this cancer.

19. Keep your blood pressure lower than 129/85 (both numbers are important, and optimal BP is < 120/80), no matter your age. The longest study (25 years follow-up on 10,874 patients) showed that Life expectancy was shortened by 2.2 years for men with high-normal blood pressure and by 4.1 years for those with stage 1 hypertension, where high-normal is a reading of 130-139 (systolic pressure) over 85-89 (diastolic pressure) and stage 1 hypertension is 140-159 over 90-99. A DASH diet (low salt, low fat, high vegetables and fruit diet) can lower your blood pressure by 7 to 11 mm Hg. Note that caloric restriction does this by its nature: by reducing the amount of calories there is usually a natural reduction in the amount of fat and salt intake – another good reason to practice caloric restriction, if you need one. In practice those who practice caloric restriction typically seem to drop their blood pressure by 10-20 mm Hg! Two other methods that seem to have merit in reducing BP are moderate exercise and reducing alcohol intake.

Things I think are worth trying because they probably work or may work

20. Consider taking some sort of non-steroidal anti-inflammatory drug (NSAID) such as Motrin. This probably reduces the risk for Alzheimer's disease and cataracts. Low-dose aspirin appears not to do this. A recent study from Holland of 7000 people (NEJM, 2001-11-22) showed an 80% drop in the incidence of Alzheimer’s for those taking NSAIDs for more than 2 years. Low dose worked as well as high dose. Another study showed that Motrin has a direct effect preventing the production of the protein associated with Alzheimer’s. The National Institute on Aging (NIA) launched a new clinical trial at the end of January 2001, called the Alzheimer’s Disease Anti-Inflammatory Prevention Trial (ADAPT), to test naproxen and celecoxib (Celebrex) with regards to Alzheimer’s prevention. So in 20 years we will know the answer – but that may be too late for some of us! See Ophthalmology 2001;108:1400-1408. Also, the combination of an NSAID and vitamin E reduces atherosclerosis in mice with high cholesterol levels by 80%. If you take ibuprofen (vs. Alzheimer’s disease, etc.) and aspirin (vs. heart disease), be sure to take the aspirin first and wait for about 2 hours: ibuprofen blocks the usefulness of aspirin.

Potential problems: bleeding problems, stomach upset, gastrointestinal bleed (can be very serious!), liver and kidney problems. Be careful of long-term use!! – I really am unsure on the long-term risk/benefit ratio of this one, but since I have no stomach or renal problems, the several studies indicating such a dramatic benefit have convinced me personally to take low-dose Motrin three times each day.

21. Glucosamine and chondroitin may reduce the chance of getting osteoarthritis, the most common kind of arthritis. Certainly they have been shown to reduce the symptoms. Both of these are the body's natural joint lubricants. To get these you need to take tablets. See the meta-analysis (collation of many scientific studies) in JAMA.
    The Lancet (a top British medical journal) published a study on 2001-01-27 that gives the following:
    Two hundred twelve patients with mild to moderate arthritis were randomly assigned a 1500 mg daily glucosamine sulfate supplement or a placebo for a period of three years in a double-blind trial. X-ray films of the knee were taken at the beginning and the conclusion of the study to measure joint space width, in order to assess cartilage loss. The study participants completed questionnaires in which symptoms such as pain, joint function and stiffness were scored.
    At the conclusion of the study, participants who received the placebo had significant mean and minimum joint-space narrowing, showing cartilage loss. The majority of the group of 106 patients receiving glucosamine sulfate had no significant joint-space narrowing. Evaluation of the questionnaires showed an improvement of symptoms in the glucosamine group and a worsening of symptoms in the placebo group. Even in the small group of patients who received glucosamine and experienced joint-space narrowing, symptomatic relief was noted.
    
    Potential problems: Chondroitin comes from cow cartilage; I know that one comes from Indian cows. I am therefore uncertain of the safety of these supplements with regards to "mad cow disease" when they come from sources outside the US.

22. If you are a man, donate blood regularly (about three times per year) and avoid iron supplements. Excess and even "normal" iron levels can cause an increased risk for heart attacks.
    Potential problems: 1) Ouch! 2) You may develop iron-deficiency anemia if you give too much blood. Not likely: I have been donating blood about four to six times per year and avoiding iron supplements for about 25 yr., and only recently had low iron levels.

23. Wine – the jury is still out. Purple grape juice in moderate amounts is probably good for you; if you are a man over 40 or a woman over 50 you could substitute a small glass of red wine each day. There is some evidence that alcohol itself has an independent beneficial effect in small quantities by increasing HDL levels, or possibly by the anti-AGE effect of its metabolite acetaldehyde (Proc Natl Acad Sci U S A 1999 Mar 2;96(5):2385-90 Inhibition of advanced glycation endproduct formation by acetaldehyde: role in the cardioprotective effect of ethanol. Al-Abed Y, Mitsuhashi T, Li H, Lawson JA, FitzGerald GA, Founds H, Donnelly T, Cerami A, Ulrich P, Bucala R). Red wine has the same antioxidants found in purple grape juice. Apparently white wine or other drinks with alcohol may not be helpful. Burgundy and cabernet sauvignon have the highest antioxidant level of those tested in vitro. Polyphenols may be the active component, and these may be more potent in red wine than in grape juice. In addition, for men who drink moderately at least 5 days per week there is also a 36% reduction in the incidence of diabetes (Conigrave et al, Diabetes 2001;50:2390-2395).
    Light alcohol intake also seems to be associated with a smaller risk of strokes; however the same study showed that there is dose-dependant shrinkage of the brain with alcohol use, and long-term, moderate or high intake of alcohol is one of the causes of cancer. In other words, you might have a smaller risk of strokes per se but gradually lose your brain in the process from the toxic effects of alcohol. To my gestalt, it is better if you can control your risk for stroke and heart attack by other means than alcohol (diet, aspirin, blood pressure control).
    
    Problems: Alcohol has several risks: alcoholism, especially if you are young or genetically prone to it, breast cancer (perhaps a 40% increase with moderate consumption in women), other cancers, hypertension, and stroke. These are the reasons for the age recommendations. For many people (and indeed in general!) it may not be worth drinking any wine at all. The metabolite of ethanol (acetaldehyde) is itself toxic, with hundreds of articles about its toxicity.

24. There is one study that implies we should eat lots of protein: the higher the protein, the longer the life span for both ad lib (eat-what-you-want) and caloric restricted rodents. From this post, about 75% down the message (slightly edited):

Days survived	Ad lib protein %			CR protein %
	10	22	51	10	22	51
900	8	2	6	93	116	149
1000	0	0	1	48	85	122
1200	0	0	0	5	61	91
1300	0	0	0	0	31	59
1400	0	0	0	0	11	24
1500	0	0	0	0	1	10
1600	0	0	0	0	0	3

Further, the highest-protein groups had the lowest ratios of malignant to benign tumors, and the lowest AGE-SPECIFIC tumor rates of all isocaloric groups: that is, the low-protein group had fewer cancers only because they died sooner -- their rate of tumor formation was higher. Ross and Bras (1973), “Influence of protein under-and overnutrition on spontaneous tumor prevalence in the rat." J Nutr 103: 944-63.

This is only one study, but they used a lot of animals (1600), and I know of no contradictory evidence.

25. Apparently most Americans' diet is short on chromium. The USDA recognized this and developed a compound that was safe and easily absorbed, chromium picolinate. Low chromium levels are associated with diabetes; it is postulated but unproven that taking chromium can help prevent diabetes. However, diabetes is so common and devastating that prevention may be worthwhile.

26. Reducing salt intake may decrease your risk of high blood pressure, which in turn affects heart disease and stroke. A study of actual salt intake (measured by urinary sodium excretion) as a risk factor in Lancet 2001 Mar 17;357(9259):848-51, high sodium intake predicted mortality and risk of coronary heart disease, independent of other cardiovascular risk factors, including blood pressure. The hazards ratios for coronary heart disease, cardiovascular disease, and all-cause mortality, associated with a 100 mmol increase in 24 h urinary sodium excretion, were 1.51 (95% CI 1.14-2.00), 1.45 (1.14-1.84), and 1.26 (1.06-1.50), respectively, in both men and women. There was a significant interaction between sodium excretion and body mass index for cardiovascular and total mortality; sodium predicted mortality in men who were overweight. Certainly short-term salt intake modulates blood pressure; the long-term effects in thin people are not clear to me. I still like my foods to taste good!

27. Reduce intake of highly processed and junk foods, such as boxed cookies, pudding mixes and fast food from places like McDonalds and Burger King, etc. These tend to have high quantities of partially hydrogenated oils, charred meat, and aluminum (an anti-caking agent that may be associated with neurological problems; however, aluminum is also found everywhere else including soil, cooking pots, antiperspirants, and municipal drinking water)

28. Aluminum may cause Alzheimer's disease. The evidence on this is unclear: there is some epidemiologic data to support it, and aluminum is found in Alzheimer’s brain plaques. Studies are hard to do, of course! Aluminum-based antiperspirants may be worst cause, perhaps because of absorption rates. On the other hand, aluminum-based antacids (Mylanta etc.) may be safe. Aluminum is also found in baking powder (sodium aluminum sulfate), buffered aspirin and some pickles (alum).

29. Vitamin E may reduce the risk of prostate cancer, perhaps by 1/3. See http://www4.cnn.com/2000/HEALTH/men/01/19/prostate.prevention.wmd/index.html. There are two main forms available: alpha (from nuts, etc., and very cheap as the d-alpha form at stores) and gamma (from nuts, etc.) Generally if supplements are taken (as opposed to natural sources such as nuts), the alpha form should be taken only with the gamma as well: both are needed, and too much alpha actually leads to depletion of gamma.

30. Selenium may possibly reduce overall cancer rates by up to 50% (based indirectly on just one study that needs confirmation). Selenium is a necessary part of the body’s anti-oxidant system. Glutathione peroxidase is a selenium-dependant enzyme found primarily in the cytoplasm (70%) but also in the mitochondria (30%). Requiring four selenium atoms per active molecule, this enzyme scavenges lipid peroxides throughout the membrane surfaces and quenches H₂O₂, converting it to water. Evidence exists that supplementation with selenium is able to increase the levels of glutathione peroxidase in patients. Selenium is found in nuts (especially Brazil nuts) and supplements.
    Caveat: too much can be toxic, causing hair loss and skin problems.

31. Chronic sleep deprivation (defined as < 5 ½ hours of sleep each night) may cause insulin resistance, and thus possibly diabetes. This is based on one small study of 27 men. I stand guilty! (http://www.cnn.com/2001/HEALTH/conditions/06/26/diabetes.sleep/index.html)

32. The spice turmeric has an anti-oxidant component named curcumin that may prevent colon cancer, prostate cancer, and others. More importantly, it seems to help prevent Alzheimer’s disease. In India where turmeric is a major spice (as a component of curry), the incidence of Alzheimer’s is quite low. In addition, rats fed curcumin had a lower rate of amyloid buildup and better memories than untreated rats.

33. Get enough vitamin D, especially if you drink a lot of milk. The Physicians’ Health Study showed a 34% increased risk in prostate cancer for those men with a high (>600 mg/day) dairy calcium intake, confirming the results of 12 of 14 epidemiological or case-control studies. This is thought to be from lowering concentrations of 1,25-dihydroxyvitamin D 3 [1,25(OH)2 D3], a hormone thought to protect against prostate cancer.
    Potential problem: too much calcium from any source may cause tissues such as the blood vessels to harden. Enough vitamin D is good; too much calcium is probably not so good.

Web site to look up the nutritional content of food (FDA)

Objections

"But I hate taking tablets and medicines."

OK, you can have the life that your grandparents had if you want. But a lot of good science in the last decade has shown many ways to improve your life, by slowing the aging process and reducing the risk of the worst and most common causes of disability and death, such as heart disease, cancer, mental illness, and arthritis. Personally, I started having children somewhat late, and I want to be healthy and active when Micah has children - I will be about 70 then. For me the potential trade-off is well worthwhile.

"But some of these things are unproven."

Do you want to wait around for the proof?

"What does it matter?"

Well, in the end, nothing. Especially when compared with the incomparable importance of salvation. Our bodies will all end up as dust; our souls are eternal. Nevertheless, although nutrition and health are not worth obsessing about, I think it is worth a little effort to live properly here on earth.

"God will take me when he wants."

Yes. But if I told you that you could reduce your risk of dying from an auto accident by buckling your seat belt, would you do it? Of course you would. We all avoid risks such as smoking or walking in the middle of a busy highway, and do things for our health such as taking medicine when we need it. These measures are similar. Do you eat certain foods because they are good for you? Then why not eat those that have been scientifically shown to be good for you, and in a way that is scientifically proven in all studied species to be best (caloric restriction)?

Also… if you follow caloric restriction and eat less, you could save on grocery expenses. Probably this will be eaten up by supplements you purchase, depending on your choices.

Other possible supplements

I simply do not have enough reliable information on these things to comment, but they look promising based on various claims. I await better studies.

ALT-711 may reverse glycation. It is currently under clinical trials as a treatment for reducing the stiffness of arteries and thus reducing systolic blood pressure: early results are promising. If there are few serious side effects, my guess is that it will probably be on the prescription drug market in the next several years.

Hormone replacement therapy for those older than age 50 (natural production of hormones such as melatonin, growth hormone, sex hormones, etc. decline dramatically at about this age, possibly with detrimental effects).

Warnings

This is NOT medical advice, which would require evaluation of you personally by your doctor. Indeed, some of these approaches (such as caloric restriction) could cause harm or even death to someone with an underlying health problem. Disclaimer: The opinions expressed are not medical advice. They are the private opinions of the author, and are not those of the Navy, the Department of Defense, or the US Government.

Some of these things are likely to prove useless or even harmful with time. Others will turn out to counter each other. Careful scientific studies on people are very hard to do, and even harder to do with nutrition.

Many of these food and supplement changes can have side effects, such as stomach upset, gas, etc. Aspirin, vitamin E, and Motrin can cause increased bleeding from surgical procedures, and even increase the risk of stroke in some. Because of this I suggest that if you adopt these suggestions, do so gradually so that if one causes you problems you can avoid it. Also, if you already have a medical problem, check with your doctor before starting vitamin or OTC medicine supplements.

Some of the supplements or diet modifications may interfere with each other. For example, two of the apparently most important factors are omega-3 fats (fish oil, etc.) and non-steroidal anti-inflammatory medications (NSAIDs: aspirin, Motrin, etc.) are thought to have beneficial effects due to their action on prostaglandins. However, omega-3 fats are precursors to the prostaglandins, while NSAIDs stop the conversion of precursors into prostaglandins. The effects of combining the two are unclear. In this case, fortunately there is a prospective trial that partially answers the question, the Lyon Diet Heart Study. To quote from this study in a discussion of the independent effects of aspirin use, cholesterol, and hypertension, “the data indicate that neither the Mediterranean dietary pattern nor any major bias has altered the usual and expected relationships between the major risk factors of CHD and recurrence.” (CHD = coronary heart disease). Other evidence that combining the most important diet modifications have added positive effects can be found in the following studies:

1. Life Span Is Prolonged in Food-Restricted Autoimmune-Prone (NZB x NZW)F(1) Mice Fed a Diet Enriched with (n-3) Fatty Acids showed that caloric restriction and fish oil had independent, positive effects on life span. Either one by itself increased life span of this mouse species by approximately 50%; combining the two nearly doubled the life span!

2. As noted in the section on getting enough protein above, Ross and Bras (1973), “Influence of protein under-and overnutrition on spontaneous tumor prevalence in the rat." J Nutr 103: 944-63 showed that combining caloric restriction with super-normal amounts of protein had an additive positive effect on life span.