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Table 2-AGE content of common foods

Source: Vlassara, H.  et al.   Advanced glycoxidation end products in commonly consumed foods. J. Am Diatetic Assoc. Aug. 2004; 104 (8): 1287-1291. (http://missclasses.com/mp3s/Prize%20CD%202010/Cooking/sdarticle.pdf)

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Then and Now: Going Paleo (Part 1)

Most people would be surprised to learn that 72.1% of the total daily energy consumed by all the people in the United States come from foods that were not part of the diet of our hunter-gather ancestors. These foods include dairy products, cereals, refined sugars, refined vegetable oils and alcohol  (http://www.ajcn.org/content/81/2/341.full.pdf).  If you include in the analysis the fact that meat today is laden with harmful antibiotics, bacteria and hormones and is much higher in saturated fat and much lower in the beneficial omega-3 and omega-9 fats than wild or paleolithic meat, then the number gets closer to 100%. The number gets even closer to 100% if you count the often fructose laden fruit commonly available at the local supermarket. To make matters even worse three of the major food companies in the U.S. are owned or were owned by cigarette companies or cigarette company stockholders (http://news.bbc.co.uk/2/hi/business/806105.stm , http://en.wikipedia.org/wiki/General_Foods). The USDA food pyramid, although it points in the right general direction, overemphasizes grains, possibly because of cost issues or because the US is a major supplier of grains to the rest of the world. Dr. Memet Oz, possibly America’s best known nutritionist, enunciates the problem rather well: Americans spend two to four times as much on health care as Mexico, China, Japan, India and most of Europe and have two to four times as much chronic disease.  We are facing an obesity, diabetes, cardiovascular disease and cancer epidemic in this country that rivals the bubonic plague of the middle ages. The economic consequences could be disastrous (http://www.sfexaminer.com/news/health/2011/09/flatten-your-belly-fix-economic-crisis-and-get-rich-all-once#ixzz1iLS8oijH ). To overcome this problem, I am not advocating going back to the 1970’s, 1900’s , or even the 1600’s (possible milestones in the epidemic of processed foods), I am advocating going back as much as 2 and 1/2 million years to a world that was radically different from today’s world. It is that world that shaped the human genome.

How the paleolithic diet/lifestyle differed from today’s diet/lifestyle  can be understood by looking at a number of different nutritional and lifestyle parameters:

Dairy Foods

About 10.6% of today’s Western diet calories comes from dairy foods. There is direct chemical evidence for dairying only going back to about 6100 BP (before the present). Milk is highly insulinotropic (insulin producing), with insulin indexes that are comparable to white bread. The insulinotropic effects of milk and yogurt are 3 to 6 times  greater than the corresponding glycemic indices (respectively), although both have very low glycemic (blood sugar raising) indices. Milk has a glycemic index that is twice that of yogurt. Yogurt is a good source of calcium, beneficial bacteria (probiotics), and protein and contains no fructose. One serving  contains about 1/500 as much glycotoxins or AGE’s as a serving of roasted chicken (Table 1).  Yogurt is slightly acidic (http://thepaleodiet.com/nutritional-tools/acid-base-balance). It is a probably a good idea to either eliminate dairy products from your diet or limit dairy to a cup or two a day of sugar free preferably organic yogurt. Cheese is a much bigger problem. It is often high in cholesterol raising saturated fat, tends to be highly acidic and, gram for gram, contains the same level of glycotoxins as roasted chicken (Table 1). I don’t have any data on whey protein at the present time but my guess is that it is substantially less insulinogenic than yogurt (no lactic acid) and significantly lower in AGE’s (no fat) than roasted chicken particularly if it is cold-processed (ie 99% not denatured protein). It has been shown to promote fat loss and muscle gain if it is consumed before a bout of exercise. Hence it is a favorite of body builders. A final problem  is that all dairy products contain peptide sequences that can trigger auto-immune responses (http://www.mercola.com/article/carbohydrates/paleolithic_diet.htm).

Cereals

About 23.9% of todays western diet calories come from cereal grains. In the U.S. 85.3% of these grains are highly processed. Before the Epi-Paleolithic (11,000 years ago), humans consumed very little or no grains. Refined grains such as bread, pasta, white flour or white rice tend to be low in fiber and have a high glycemic index, a measure of how quickly a food will drive up  a person’s blood sugar and (indirectly) insulin levels. Chronically high insulin levels can interfere with a hormone called leptin that tells the brain how much fat is on board and suppresses appetite. (http://www.mattmetzgar.com/matt_metzgar/files/obesitystarvation.pdf). This leads to obesity and insulin resistance. Insulin resistance is a driving factor behind the metabolic syndrome.  It is a no-brainer that you should eliminate flour from your diet or greatly reduce it. It is not so obvious that you should eliminate or significantly reduce whole grains as well. Whole grains contain anti-nutrients  such as phytates, alkylresorcinols, protease inhibitors, and lectins that can suppress the absorption of valuable vitamins and minerals such as niacin, calcium, iron, magnesium, and zinc (http://www.healthy-eating-politics.com/phytic-acid.html). Like dairy, grains contain peptide (or protein) sequences that may stimulate autoimmune responses (http://www.mercola.com/article/carbohydrates/paleolithic_diet.htm). The whole grains  contain anti-nutrients called lectins (specifically wheat germ agglutinin-WGA)  can also stimulate the influx of dietary antigens (including dietary proteins found in dairy, grains and legumes that mimic the body’s collagen) into the blood stream that can set off an autoimmune response. The end result is that the body loses its ability to distinguish self from non-self. Hence if you have autoimmune problems, eliminating grains would probably be particularly useful. One exception to at least some of the problems with grains is Ezekiel bread, which contains sprouted whole grains and no flour. The sprouting eliminates the lectins and anti-nutrients but probably has little effect on the immune system provoking proteins or peptides.

Refined Sugars

Refined sugars constitute about 18.6% of the calories in the western diet (http://www.science20.com/news_articles/us_sugar_consumption_rise)  and of course 0% of the paleolithic diet. However paleolithic humans consumed small amounts of honey. Among  the Ache Indians of Paraguay, honey represented about 3% of total daily intake over a 4 year period. Table sugar (sucrose) and high fructose corn syrup are major constituents of the modern western diet. Both are combinations of fructose and glucose. Glucose is relatively benign although it may cause weight gain but fructose, in excess, can cause serious health problems such as dislipidemia (leading to cardiovascular disease) and increased blood pressure (http://www.mattmetzgar.com/matt_metzgar/files/obesitystarvation.pdf and http://www.biomedcentral.com/content/pdf/1743-7075-2-5.pdf).  It is a good idea to eliminate added sugar and corn syrup from your diet. If you must have something sweet try stevia (brand name Truvia) or brown rice syrup as sweeteners. There are now many commercial products that eliminate fructose as a sweetener by replacing sucrose and corn syrup with stevia or brown rice syrup. You can also significantly reduce your intake of fructose by eliminating fruit juice. Eat berries that are very high in antioxidant plant polyphenols and compounds that suppress carbohydrate digestion. Acai berries are a very good choice because they contain no fructose and top the charts for antoxidant capacity. There are a number of brands that can be found in the frozen fruit section of your natural foods store. A fundamental problem is that any sweet tasting food will lead to increased calorie consumption because the brain registers sweetness separately from other food sensations (http://www1.appstate.edu/~dennistonjc/Hunger_eating_and_ill_heath.pdf) In one study a group of rats were given additional bread and chocolate in their diet. As a result their caloric intake increased by 84% and within 120 days their body weights had increased by an average of 49%(Rogers, P. J., & Blundell, J. E. (1980). Investigation of food selection and meal parameters during the development of dietary induced obesity[Abstract]. Appetite, 1, 85.)!

The bottom line is that to lose weight and improve your health cut back on fructose (especially in juice) and on sweet foods in general. Eliminate or greatly reduce refined sugar and corn syrup from your diet. A huge variety of foods contain refined sugar-most baked goods (cookies, cakes,  pies), most candy, most ice cream including soy ice cream and many, many other refined foods.)

YouTube channel about exercise

I have added a YouTube channel to this blog:  http://www.youtube.com/playlist?list=PL6731500FD430911E&feature=plcp

 

Table 1

Fats AGEs (U/g) Serving (g) AGEs/serving (kU)
Almonds, roasted 66,514 30 1,995
Avocado 15,772 30 473
Butter 264,873 5 1,324
Cashews, roasted 98,082 30 2,942
Cream cheese, Philadelphia soft 108,843 30 3,265
Margarine, 60% vegetable oil 175,192 5 876
Mayonnaise 94,010 5 470
Mayonnaise, imitation 2,000 5 10
Mayonnaise, low fat 22,011 5 110
Olive, ripe 16,686 30 501
Peanut butter, smooth 75,183 30 2,255
Walnuts, roasted 78,874 30 2,366
Salad dressing, Caesar 7,371 15 111
Salad dressing, French, Lite 11 15 0
Salad dressing, Italian, Lite 8 15 0
Beef AGEs (U/g) Serving (g) AGEs/serving (kU)
Frankfurter, boiled 7 min 74,850 90 6,736
Frankfurter, broiled 5 min 112,697 90 10,143
Hamburger, fried 6 min 26,391 90 2,375
Hamburger, fast food 54,176 90 4,876
Meatball, boiled in sauce 1 h 28,519 90 2,567
Meat loaf, crust off, roasted 45 min 18,619 90 1,676
Roast beef 60,708 90 5,464
Shoulder cut, boiled 1 h 22,305 90 2,007
Shoulder cut, broiled 15 min 59,636 90 5,367
Bacon, microwave 3 min 90,228 13 1,173
Deli ham, smoked 23,491 90 2,114
Pork chop, pan fried 7 min 47,526 90 4,277
Beef and pork links, pan fried 54,255 45 2,441
Sausage, pork links, microwave 1 min 59,438 90 5,349
Poultry AGEs (U/g) Serving (g) AGEs/serving (kU)
Chicken breast, skinless cubes, pan fried 15 min 61,221 90 5,510
Steamed 10 min and broiled 12 min 56,348 90 5,071
Pan fried 10 min and boiled 12 min 63,398 90 5,706
Chicken breast, skinless cutlet, raw 7,686 90 692
Boiled 1 h 11,236 90 1,011
Broiled 15 min 58,281 90 5,245
Fried 8 min 73,896 90 6,651
Microwave 5 min 15,245 90 1,372
Chicken breast, with skin, roasted 45 min 60,203 90 5,418
Chicken, dark meat, broiled 1 h 82,992 90 7,469
Chicken loaf, roasted, crust off, 45 min 14,195 90 1,278
Chicken nuggets 86,271 90 7,764
Turkey breast, cubes, skinless, broiled 55,747 90 5,017
Turkey breast steak, skinless, broiled 43,873 90 3,949
Smoked turkey breast, seared 60,137 90 5,412
Fish AGEs (U/g) Serving (g) AGEs/serving (kU)
Fish loaf, boiled 90 min 7,606 90 685
Salmon, breaded, broiled 10 min 14,973 90 1,348
Salmon, raw 5,573 90 502
Salmon, smoked 5,718 90 515
Trout, raw 7,830 90 705
Trout, roasted 25 min 21,383 90 1,924
Tuna, loaf, roasted 40 min 5,895 90 531
Roasted 25 min 9,189 90 827
White, canned in oil, Albacore 17,396 90 1,566
Cheese AGEs (U/g) Serving (g) AGEs/serving (kU)
American, processed 86,775 30 2,603
American, processed, low fat 40,395 30 1,425
Brie 55,979 30 1,679
Cottage cheese 1% fat 14,532 120 1,744
Feta 84,235 30 2,527
Mozzarella, part skim 16,777 30 503
Parmesan, grated 169,020 15 2,535
Swiss, processed 44,701 30 1,341
Eggs AGEs (U/g) Serving (g) AGEs/serving (kU)
Egg yolk, boiled 10 min 12,134 15 182
Boiled 12 min 18,616 15 279
Egg white, boiled 10 min 442 30 13
Boiled 12 min 573 30 17
Egg, fried with margarine 27,494 45 1,237
Tofu AGEs (U/g) Serving (g) AGEs/serving (kU)
Broiled 41,067 90 3,696
Raw 7,875 90 709
Sautéed 38,303 90 3,447
Breads AGEs (U/g) Serving (g) AGEs/serving (kU)
Bagel 1,075 30 32
Greek, hard 1,514 30 45
Whole wheat, center 536 30 16
Whole wheat, center toasted 1,080 30 25
Whole wheat, crust 730 30 22
Whole wheat, crust, toasted 1,394 30 36
Breakfast foods AGEs (U/g) Serving (g) AGEs/serving (kU)
Pancake, frozen, toasted 22,618 30 679
Pancake, homemade 9,722 30 292
Waffle, frozen, toasted 28,711 30 861
Cereals AGEs (U/g) Serving (g) AGEs/serving (kU)
Bran Flakes 346 30 10
Corn Flakes 2,320 30 70
Frosted Flakes 4,270 30 128
Corn Pops 12,431 30 373
Oatmeal instant, dry 188 30 4
Oatmeal, instant with honey 175 175 31
Rice Krispies 19,997 30 600
Grains and legumes AGEs (U/g) Serving (g) AGEs/serving (kU)
Bean, red kidney, raw 1,158 100 116
Bean, red kidney, canned 1,906 100 191
Bean, red kidney, cooked 1 h 2,983 100 298
Pasta, cooked 8 min 1,123 100 112
Pasta, spiral, cooked 12 min 2,420 100 245
White rice, quick cook, 10 min 88 100 9
White rice, converted, cooked 35 min 91 100 9
Starchy vegetables AGEs (U/g) Serving (g) AGEs/serving (kU)
Corn, canned 195 100 20
Sweet potato, roasted, 1 h 723 100 72
White potato, boiled, 25 min 174 100 17
White potato, french fries, homemade 6,939 100 694
White potato, french fries, fast food 15,219 100 1,522
Crackers and snacks AGEs (U/g) Serving (g) AGEs/serving (kU)
Chips, corn, Doritos 5,049 30 151
Lay’s Potato Chips 28,818 30 865
Chips Ahoy Chocolate Chip Cookies 16,837 30 505
Oatmeal raisin cookie 13,707 30 411
Cracker, Goldfish, cheddar 21,760 30 653
Chocolate Chunk Granola Bar 5,068 30 152
Peanut Butter Chocolate Chunk Granola Bar 31,761 30 953
Popcorn with butter, air popped 1,340 30 40
Fruits AGEs (U/g) Serving (g) AGEs/serving (kU)
Apple 127 100 13
Apple, baked 445 100 45
Banana 87 100 9
Cantaloupe 201 100 20
Raisin 201 30 36
Vegetables AGEs (U/g) Serving (g) AGEs/serving (kU)
Broccoli, carrots, celery, grilled 2,260 100 226
Carrots, canned 103 100 10
Green beans, canned 179 100 18
Onion, raw 358 100 36
Tomato, raw 234 100 23
Other carbohydrates AGEs (U/g) Serving (g) AGEs/serving (kU)
Sugar, white 0 5 0
Sugar substitute, powder 58 1 0
Milk and milk products AGEs (U/mL) Serving (mL) AGEs/serving (kU)
Milk, whole 48 250 12
Fat free 5 250 1
Fat free, microwave, 1 min 21 250 5
Fat free, microwave, 3 min 345 250 86
Formula, infant 4,861 30 146
Human milk, fresh 52 30 2
Instant, chocolate, skim milk, sugar free 11 120 1
Yogurt, strawberry or cherry, nonfat, sugar free 40 250 10
Syrups, gels and juices AGEs (U/mL) Serving (mL) AGEs/serving (kU)
Honey 87 15 1
Syrup, caramel, sugar free 15 15 0
Dark corn 14 15 0
Apple 20 250 5
Cranberry 32 250 8
Orange, fresh squeezed 3 250 1
Orange, carton 56 250 14
Dishes AGEs (U/g) Serving (g) AGEs/serving (kU)
Italian pasta salad, homemade 9,346 100 935
Macaroni and cheese, baked 40,698 100 4,070
Pizza, thin crust 68,248 100 6,825
Sandwich, toasted cheese 43,327 100 4,333
Beverages AGEs (U/mL) Serving (mL) AGEs/serving (kU)
Coffee, decaffeinated, instant 53 250 13
Instant 47 250 12
Drip method 15 250 4
On a heating plate more than 1 h 134 250 34
With milk 66 250 17
With milk and sugar 24 250 6
Cola 65 250 16
Cola, sugar free 12 250 3
Tea 19 250 5
Condiments AGEs (U/mL) Serving (mL) AGEs/serving (kU)
Ketchup 103 15 2
Mustard 29 15 0
Soy sauce 573 15 9
Vinegar, balsamic 352 15 5
Vinegar, white 377 15 6

Source: Vlassara, H.  et al.   Advanced glycoxidation end products in commonly consumed foods. J. Am Diatetic Assoc. Aug. 2004; 104 (8): 1287-1291. (http://missclasses.com/mp3s/Prize%20CD%202010/Cooking/sdarticle.pdf)

Introduction

The distinctive features of the human genome or genetic program evolved in an era of some two and one half million years known as the paleolithic era (early stone age).  This era ended about 10,000 B.C.E. During this period,  food was often scarce, unpredictable and also often not very diverse. There was no electricity and little interior lighting, so sleeping and waking was entrained to the sun/moon light/dark cycle. Obtaining food usually required a considerable expenditure of physical energy by hunting or foraging. Like other mammals, to guard against future shortages, we evolved the capacity to store excess calories when food was diverse and abundant. Today a vast diverse abundance of food is always readily available. For most of us, obtaining our food requires the expenditure of a modest amount of mental but little physical energy. Much of the modern diet is “pre-digested” in the form of powdered grains, refined sugars and liquified pre-frozen fruits so that we do not even have to expend energy to digest our food.  This mismatch between our hunter-gatherer genome and our modern sedentary processed food lifestyle is thought to have resulted in a worldwide epidemic in the diseases of civilization or metabolic syndrome diseases such as prolonged obesity/sarcopenia (fat gain and loss of lean body mass such as muscle and bone), cardiovascular disease,  type 2 diabetes, hypertension and dislipidemia (elevated serum triacyglycerols (triglycerides), small-dense LDL cholesterol and reduced HDL cholesterol). Hence to optimize our biology and health, it is thought that we must return to the rhythms and patterns of our pre-industrial, pre-agricultural ancestors without abandoning the spectacular advances that technology has brought about.

Another source of inspiration for those who are seeking to optimize their health and biology are  laboratory experiments that seek to maximize health and longevity in animals ranging from yeast cells to rhesus monkeys by restricting calories or specific nutrients.

Comparison of restricted and unrestricted rhesus monkeys

The above picture compares unrestricted rhesus monkeys (A-B) with restricted monkeys (C-D) at an average lifespan age.  Restricted animals, such as these monkeys, are often astoundingly robust, healthy and long-lived but also chronically hungry, a kind of blessed/wretched state that few humans have so far attempted to emulate.  To overcome this hunger obstacle,  scientists have proposed various strategies for tricking the hunger mechanism into requiring fewer calories.  On a similar front, others are seeking to identify small molecules that will activate the health and life-span promoting signaling pathways that are activated by calorie restriction. One such candidate calorie restriction memetic, resveratrol, has turned out to be mostly hot air and wishful thinking, but the search continues.

The picture represents the tradeoff between growth and longevity. At least one dwarf mouse of the type shown on the right lived nearly five years more than twice the lifespan of the species.

Another intriguing area of aging research involves the genetic engineering of test animals with modifications that typically reduce the production of growth promoting compounds such as insulin, insulin like growth factor or growth hormone or that downregulate the receptors to these hormones or the signaling pathways  that are downstream to these receptors. One such animal., the GHR-KO Dwarf Mouse 11C, very nearly lived 5 years or the human equivalent of 180 to 200 years. This mouse was born at the Southern Illinois University vivarium on January 15, 1998 and died about one week short of 5 years later. At the time of his death he weighed only 8 grams, small even for a dwarf mouse. Apparently there is a trade off between growth and longevity. The researchers hypothesized that the long life of the GHR-KO Dwarf mice is partly related to their low levels of glucose and insulin. At a deeper level the long life of these genetically modified mice as well as calorie restricted mice is apparently partly related to downregulation of  the mTOR gene/protein and the upregulation or activation of the SIRT1 signaling gene/protein.  mTOR suppression promotes autophagy, the breakdown and removal of old broken down mitochondria, oxidized proteins and AGE’s or advanced glycation end products. AGE’s are protein-sugar molecules that can build up in cells and tissues over time causing cell senescence and aging. Old broken down mitochondria can be a major source of DNA damaging free radicals. Oxidized proteins can disrupt the the cell signaling system of the cell. Sirt1 activation results in slower aging by decreasing oxidative damage to cellular DNA and by increasing DNA repair mechanisms.

On still another front, researchers hope to renew tissues and even entire organs using the technologies of genetic engineering and regenerative medicine. One fascinating possibility is that the immune system, red blood cells and the inner layer of blood vessels could be renewed by replacing the bone marrow stem cells that form these immune and blood/vascular tissues.

If you are searching for a way to apply these calorie restriction/genomic harmony ideals to your own wellness strategy, then the key concepts may be as follows:

(1) Adopt the lifestyle of your Paleolithic ancestors.  Eat the kind of food that they ate and mimic their patterns of food consumption. If you do this correctly you will most likely substantially reduce the total number of calories you consume relative to the calories you expend. In so doing  you will very likely not only lose a lot of weight, you will also improve a wide range of health parameters including the highly important aging parameters that are slowed by calorie restriction. You will very likely switch the signaling patterns in your body’s cells from growth/fat storage/reproduction mode to maintenance/repair mode. This latter pattern is synonymous with robust health and slowed aging.  On the negative side, it does not prepare you for future food shortages or famines!  In the 21st century, future food shortages associated with reduced income can be avoided by various economic measures. The body’s stone age “intelligence” or genome has not yet caught up with this, so it continues to pile on the pounds in anticipation of the coming famine. Over time there is a dramatic shift in the body’s physiology towards disease and disfunctionality.

(2) Sleep the way your ancestors slept and expend energy or exercise in a way that mimics their lifestyle.

(3) I am not suggesting that you need to eat the exact same foods that our ancestors ate. Rather the idea is to mimic the nutrient pattern of the paleolithic era as a first approximation to an ideal diet. A second approximation would be to follow a diet that matches the best cutting edge research. A third and probably even better approximation would be to select an individual diet that minimizes disease and maximizes your individual physiological measures of wellness. In other words what works best for you is the bottom line. The main drawback of this individualized approach is that it may be somewhat difficult to measure health parameters.

(4) In selecting an ancestor to emulate, do not select one who was living under conditions of great nutrient abundance and diversity. This ancestor was  no doubt in a kind of fat storage, cell growth and reproductive signaling mode. He/she was probably not exercising too much. Instead emulate the ancestor who had a real perpetual need to hunt or gather because food was always both scarce and often not too diverse. This hypothetical model ancestor was consuming a diet that was nutrient dense but calorically deficient. It was nutrient balanced and symmetric in the long term but unbalanced and asymmetric in the short term. This hypothetical ancestor was perpetually lean but very well nourished and was switched over into a maintenance/repair signaling pattern that is correlated with robust health and longevity.

(5) Do all of the above while also applying the best discoveries of modern medical science.

(6) Finally the above prescriptions for healthy living are in no way one-size-fits-all. If you are someone who experiences high uric acid levels and consequent activation of fat storage signaling pathways in response to excessive  purine rich protein/meat, then you may need to limit your consumption of purine rich meats.  If you are part of the 10% of the population that is fat-insensitive, meaning that your brain does not respond to fat by decreasing hunger, then a low fat version of this diet would be best for you.  If you are part of the 40% of the population that is grain sensitive, then you need to be zealous about restricting grains, especially the non-sprouted variety. If you are ethically opposed to the use of animals for food even if they are treated humanely, then you will want to put together a vegetarian version of the diet prescriptions of this blog. In the not too distant future maybe artificial intelligence expert systems (“health bots”) will be able to customize a diet, exercise and lifestyle regimen that will fit each person’s unique physiology, monitor that physiology over time, and make recommendations for changes.

Further reading:

Colman, R. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 2009;325(5937): 201-204.

Cordain, L. Origins and evolution of the Western diet: health implications for the 21st century. Am J Clin Nutr 2005; 81:341-354. (http://www.ajcn.org/content/81/2/341.full.pdf)

Johnson, Richard J. et al. Lessons from comparative physiology: could uric acid represent a physiologic alarm signal gone awry in western society? J Comp Physiol. 2009 January; 179(1):67-76

Pinel, J. P. J. Hunger, Eating, and Ill Health. American Psychologist 2000; 55(10): 1105-1116.(http://www1.appstate.edu/~dennistonjc/Hunger_eating_and_ill_heath.pdf)

Stipp, David. A new path to longevity. Scientific American,  January 2012.

Varady, K.A. Alternate-day fasting and chronic disease prevention: a review of human and animal trials. Am J Clin Nutr 2007;86:7-13.