Endnotes Chapters 6,7,8,9,10

Chapter 6
1 Diet is key because humans do not synthesize either essential fatty acid. See, for example, A. P. Simopoulos. 2002. “The importance of the ratio of omega-6/omega-3 essential fatty acids.” Biomed Pharmacother. Oct;56(8): 365–379; M. Crawford et al. 2000. “Role of plant-derived omega-3 fatty acids in human nutrition.” Ann Nutr Metab. 44(5–6): 263–265.
2 F. B. Hu and M. J. Stampfer. 1999. “Nut consumption and risk of coronary heart disease: a review of epidemiologic evidence.” Curr Atherscler Rep. Nov;1(3): 204–209. Other epidemiological studies also support this finding. See J. L. Ellsworth et al. 2001. “Frequent nut intake and risk of death from coronary heart disease and all causes in postmenopausal women in the Iowa Women’s Health Study.” Nutr Metab Cardiovasc Dis. Dec;11(6): 372–377. A plethora of important insights about nutrition have come from this study (see www.channing.harvard.edu/nhs/pub.html).
3 “There is increasing evidence that inflammation is also involved in the atherogenic process.” J. T. Kuvin and R. H. Karas. 2003. “The effects of LDL reduction and HDL augmentation on physiologic and inflammatory markers.” Curr Opin Cardiol. Jul;18(4): 295–300. See also T. Pischon et al. 2003. “Habitual dietary intake of n-3 and n-6 fatty acids in relation to inflammatory markers among US men and women.” Circulation. Jul 15;108(2): 155–160.
4 Omega-3 fatty acids, for example, affect myocardial contractility, blood pressure, and coagulation factors. They have also been shown to prevent “sudden death after myocardial infarction.” D. Bhatnagar and P. N. Durrington. 2003. “Omega-3 fatty acids: their role in the prevention and treatment of atherosclerosis related risk factors and complications.” Int J. Clin Pract. May;57(4): 305–314; F. Thies. 2003. “Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomized controlled trial.” Lancet. Feb 8;361(9356): 477–485.
5 An appraisal of “33 published case-control and cohort studies that examined the relationship between prostate cancer and dietary fat or specific fatty food types” found eight studies that “suggested a statistically significant association, and many studies noted significant associations for specific types of fatty foods (e.g., milk or meat) and prostate cancer.” N. Fleshner et al. 2004. “Dietary fat and prostate cancer.” J Urol. Feb;171(2 Pt 2): S19–24; L. N. Kolonel, A. M. Y. Nomura, and R. V. Cooney. 1999. J Natl Cancer Inst. 91(5): 414–428; L. M. Newcomer et al. 2001. “The association of fatty acids with prostate cancer risk.” Prostate. Jun 1;47(4): 262–268.
6 Y. Park and W. S. Harris. 2003. “Omega-3 fatty acid supplementation accelerates chylomicron triglyceride clearance.” J Lipid Res. Mar;44(3): 455–463; W. S. Harris. 1997. “n-3 fatty acids and serum lipoproteins: human studies.” Am J Clin Nutr. May;65(5 Suppl): 1645S–1654S.
7 A. H. Lichtenstein. 2003. “Dietary fat and cardiovascular disease risk: quantity or quality?” J Womens Health (Larchmt). Mar;12(2): 109–114.
8 H. Chen et al. 2003. “EPA and DHA attenuate ox-LDL-induced expression of adhesion molecules in human coronary artery endothelial cells.” J Mol Cell Cardiol. Jul;35(7): 769–775; S. Renaud and D. Lanzmann-Petithory. 2002. “Dietary fats and coronary heart disease pathogenesis.” Curr Atheroscler Rep. Nov;4(6): 419–424.
9 A. Nordoy et al. 2001. “n-3 polyunsaturated fatty acids and cardiovascular diseases.” Lipids. 36 Suppl: S127–129; K. Imaizumi et al. 2000. “Role of dietary lipids in arteriosclerosis in experimental animals.” Biofactors. 13(1-4): 25–28; J. A. Conquer et al. 1999. “Effect of supplementation with dietary seal oil on selected cardiovascular risk factors and hemostatic variables in healthy male subjects.” Thromb Res. 1;96(3): 239–250.
10 P. C. Calder. 2002. “Dietary modification of inflammation with lipids.” Proc Nutr Soc. Aug;61(3): 345–358; P. Yang et al. 2002. “Quantitative high-performance liquid chromatography/electrospray ionization tandem mass spectrometric analysis of 2- and 3-series prostaglandins in cultured tumor cells.” Anal Biochem. Sep 1;308(1): 168–177.
11 L. A. Sauer et al. 2000. “Mechanism for the antitumor and anticachectic effects of n-3 fatty acids.” Cancer Res. Sep 15;60(18): 5289–5295.
12 P. M. Kris-Etherton et al. 2002. “Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease.” Circulation. Nov 19;106(21): 2747–2757. An article by two of the authors (W. S. Harris and L. J. Appel) is also available on the AMA site (www.americanheart.org).
13 M. E. Surette. 2003. “Inhibition of leukotriene synthesis, pharmacokinetics, and tolerability of a novel dietary fatty acid formulation in healthy adult subjects.” Clin Ther. Mar;25(3): 948–971; L. S. Harbige. 2003. “Fatty acids, the immune response, and autoimmunity: question of n-6 essentiality and the balance between n-6 and n-3.” Lipids. Apr;38(4): 323–341.
14 D. Bagga et al. 2003. “Differential effects of prostaglandin derived from omega-6 and omega-3 polyunsaturated fatty acids on COX-2 expression and IL-6 secretion.” Proc Natl Acad Sci USA. Feb 18;100(4): 1751–1756.
15 T. van Vliet and M. B. Katan. 1990. “Lower ratio of n-3 to n-6 fatty acids in cultured than in wild fish.” Am J Clin Nutr. Jan;51(1): 1–2. There are a variety of other issues associated with farming salmon. See, for example, M. D. Eason et al. 2002. “Preliminary examination of contaminant loadings in farmed salmon, wild salmon and commercial salmon feed.” Chemosphere. Feb;46(7): 1053–1074.
16 M. Massaro et al. 2002. “Quenching of intracellular ROS generation as a mechanism for oleate-induced reduction of endothelia activation and early atherogenesis.” Thromb Haemost. Aug;88(2): 335–344; C. M. Williams. 2001. “Beneficial nutritional properties of olive oil: implications for postprandial lipoproteins and factor VII.” Nutr Metab Cardiovasc Dis. Aug;11(4 Suppl): 51–56.
17 “Progression of CAD over 39 mo, measured by a decrease in minimum absolute width of coronary segments (MinAWS) on angiography, was highly correlated with intakes of palmitic, stearic (18:0), palmitoleic, and elaidic (t-18:1) acids (P , 0.001) . . . ”
“Our results indicate that three nonessential fatty acids—stearic acid, palmitoleic acid, and omega 9 eicosatrienoic acid, and one essential fatty acid—dihomogammalinolenic acid, are independent correlates of blood pressure among middle-aged American men at high risk of coronary heart disease.”
Center for Science in the Public Interest, July/August Nutrition Action Newsletter, using the USDA Nutrient Database for Standard Reference (Release 14) as a source.
18 T. Thostrup et al. 1994. “Fat high in stearic acid favorably affects blood lipids and factor VII coagulant activity in comparison with fats high in palmitic acid or high in myristic and lauric acids.” Am J Clin Nutr. Feb;59(2): 371–377.
19 F. Joffre et al. 2001. “Kinetic parameters of hepatic oxidation of cyclic fatty acid monomers formed from linoleic and linolenic acid.” J Nutr Biochem. Oct;12(10): 554–558; B. Potteau. 1976. “Influence of heated linseed oil on reproduction in the female rat and on the composition of hepatic lipids in young rats.” Ann Nutr Aliment. 30(1): 67–88.
20 J. K. Donnelly and D. S. Robinson. 1995. “Free radicals in food.” Free Radic Res. Feb;22(2): 147–176.
21 Methods of commercial oil production include expeller pressing (which can generate temperatures as high as 185°F); cold pressing; and solvent extraction, in which oils are extracted using petroleum solvents.
22 A. H. Lichtenstein et al. 1999. “Effects of different forms of dietary hydrogenated fats on serum lipoprotein cholesterol levels.” N Engl J Med. Jun 24;340(25): 1933–1940.
23 N. de Roos et al. 2001. “Consumption of a solid fat rich in lauric acid results in a more favorable serum lipid profile in healthy men and women than consumption of a solid fat rich in trans-fatty acids.” J Nutr. Feb;131(2): 242–245.
24 A. Ammouche et al. 2002. “Effect of ingestion of thermally oxidized sunflower oil on the fatty acid composition and antioxidant enzyme of rat liver and brain in development.” Ann Nutr Metab. 46(6); 268–275.
25 S. M. Marcovina and M. L. Koschinsky. 2003. “Evaluation of lipoprotein(a) as a prothrombotic factor: progress from bench to bedside.” Curr Opin Lipidol. Aug;14(4): 361–366; M. Koruk et al. 2003. “Serum lipids, lipoproteins, and apolipoproteins levels in patients with nonalcoholic steatohepatitis.” J Clin Gastroenterol. Aug;37(2): 177–182.
26 R. Rosmond and P. Björntorp. 1998. “The interactions between hypothalamic-pituitary-adrenal axis activity, testosterone, insulin-like growth factor I and abdominal obesity with metabolism and blood pressure in men.” Int. J Obes Relat Metab Disord. Dec;22(12): 1184–1196.
27 S. M. Grundy et al. 2002. “Diet composition and the metabolic syndrome: what is the optimal fat intake?” Am J Med. Dec 30;113 Suppl 9B: 25S–29S.
28 “The more hydrogenated an oil is, the harder it will be at room temperature. For example, a spreadable tub margarine is less hydrogenated and so has fewer trans fats than a stick margarine.” “Fats and cholesterol,” Harvard School of Public Health (www.hsph.harvard.edu/nutritionsource/fats.html). See also F. D. Kelly et al. 2001. “A stearic acid-rich diet improves thrombogenic and atherogenic risk factor profiles in healthy males.” Eur J Clin Nutr. Feb;55(2): 88–96; C. M. Nieuwenhuys and G. Hornstra. 1998. “The effects of purified eicosapentaneoic and docosahexaneoic acids on arterial thrombosis tendency and platelet function in rats.” Biochem Biophys Acta. Feb 23;1390(3): 313–322.
29 J. W. Ju and M. Y. Jung. 2003. “Formation of conjugated linoleic acids in soybean oil during hydrogenation with a nickel catalyst as affected by sulfur addition.” J Agric Food Chem. May 7;51(10): 3144–3149; M. A. De Oliveira et al. 2003. “Method development for the analysis of trans-fatty acids in hydrogenated oils by capillary electrophoresis.” Electrophoresis. May;24(10): 1641–1647.
30 S. Vincent et al. 2003. “Targeting of proteins to membranes through hedgehog auto-processing.” Nature Biotech (advance online publication July 13); C. Thiele et al. 2000. “Cholesterol binds to synaptophysin and is required for biogenesis of synaptic vesicles.” Nature Cell Biol. Jan;2: 42–49.
31 L. Ellegård et al. 2000. “Will recommended changes in fat and fibre intake affect cholesterol absorption and sterol excretion?” Eur J Clin Nutr. Apr;54(4): 306–313.
32 I. S. Cowin and P. M. Emmett. 2001. “Associations between dietary intakes and blood cholesterol concentrations at 31 months.” Eur J Clin Nutr. Jan;55(1): 39–49.
33 Cortisol is one of several steroids (others include progesterone, estradiol, and testosterone) synthesized from cholesterol. See H. Lodish et al. 2000. “Cell-to-cell signaling: hormones and receptors.” Molecular Cell Biology. New York: W. H. Freeman and Company.
34 See Step by Step: Eating to Lower Your High Blood Cholesterol. National Institutes of
Health: National Heart, Lung, and Blood Institute; www.limcpc.com/Medical%20Info/cholest/
eattolowerchol.htm.
35 J. Scott. 1999. “Heart disease: good cholesterol news.” Nature. Aug 26;400: 816–819.
36 For further discussion on the importance of limiting dietary cholesterol consumption, see, for example, High Blood Cholesterol: What You Need to Know, National Cholesterol Education Program; www.nhlbi.nih.gov/health/public/heart/chol/hbc_what.htm; Taking Charge of Your Health: The Harvard Medical School Family Health Guide (available online at www.health.harvard.edu/fhg/fhgupdate/A/A2.shtml); R. M. Weggemans et al. 2001. “Dietary cholesterol from eggs increases the ratio of total cholesterol to high-density lipoprotein cholesterol in humans: a meta-analysis.” Am J Clin Nutr. May;73(5): 885–891.
37 Like antioxidants, ketone bodies are attracting a great deal of research interest, often around treatment for diabetes, obesity, and epilepsy (ketogenic diets for epilepsy are primarily based on fats). The following citation states that the brain can use both glucose and ketones for energy: A. E. Greene et al. 2003. “Perspectives on the metabolic management of epilepsy through dietary reduction of glucose and elevation of ketone bodies.” J Neurochem. Aug;86(3): 529–537.
38 National Institutes of Health: National Heart Lung and Blood Institute. 2001. “High blood cholesterol: what you need to know,” at www.nhlbi.nih.gov/health/public/heart/chol/wyntk.pdf (NIH Pub. No. 01-3290).
39 R. M. Anderson et al. 1996. “Transmission dynamics and epidemiology of BSE in British cattle.” Nature. 382: 779–788.
40 J. X. Kang. 2004.”Transgenic mice: fat-1 mice convert n-6 to n-3 fatty acids.” Nature. Feb 5;427(6974): 504.
41 A. Baguisi et al. 1999. “Production of goats by somatic cell nuclear transfer.” Nature Biotechnology. May 17(5): 456–461. For more information on the partnership between Genzyme Transgenics Corporation, Louisiana State University, and Tufts University School of Medicine that produced this work, see the press release on the GTC Biotherapeutics Web site, www.transgenics.com/pressreleases/pr042799.html.
42 This five-year project was announced in December 1999. Why protein folding? “The life sciences have benefited from computational capabilities and will be driving the requirements for data, network, and computational capabilities in the future. . . . The understanding of the protein folding phenomenon is a recognized ‘grand challenge problem’ of great interest to the life sciences.” F. Allen et al. 2001. “Blue Gene: A vision for protein science using a petaflop supercomputer.” IBM Sys J. 40(2): 310–327.
43 C. L. Scott. 2003. “Diagnosis, prevention, and intervention for the metabolic syndrome.” Am J Cardiol. Jul 3;92(1A): 35i–42i; F. B. Hu and W. C. Willett. 2002. “Optimal diets for prevention of coronary heart disease.” JAMA. Nov 27;288(20): 2569–2578.
44 In November 1989, FDA recalled all dietary supplements containing more than 100 mg of L-tryptophan due to over 1,500 cases of a rare, sometimes fatal condition known as EMS (eosinophilia-myalgia syndrome). See CDC. 1990. “Update: Eosinophilia-Myalgia Syndrome Associated with Ingestion of L-Tryptophan—United States, through August 24, 1990.” MMWR. Aug 31;39(34); 587–589. Subsequent investigation suggested that these cases of disease were due to contaminants introduced in the manufacture of this amino acid and not due to the amino acid itself. It is now available again in the U.S., but either by prescription or at a much increased price.
45 S. Moncada and A. Higgs. 1993. “The L-arginine-nitric-oxide pathway.” N Engl J Med. Dec 30;329(27): 2002–2012.
46 The following book cites extensive research documenting the value of arginine supplementation in maintaining healthy cardiac arteries and in avoiding heart disease and stroke: J. Zimmer and J. P. Cooke. 2002. The Cardiovascular Cure: How to Strengthen Your Self-Defense Against Heart Attack and Stroke. New York: Broadway. Also A. Lerman et al. 1998. “Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans.” Circulation. 97: 2123–2128; B. Y. Wang et al. 1999. “Regression of atherosclerosis: role of nitric oxide and apoptosis.” Circulation. 99: 1236–1241.
47 A. L. Jenkins. 2002. “Depression of the glycemic index by high levels of â-glucan fiber in two functional foods tested in type 2 diabetes.” Eur J Clin Nutr. Jul;56(7): 622–628.
48 J. W. Helge. 2002. “Prolonged adaptation to fat-rich diet and training; effects on body fat stores and insulin resistance in man.” Intl J Obesity. Aug;26(8): 1118–1124.
49 D. J. Jenkins et al. 2000. “Dietary fibre, lente carbohydrates and the insulin-resistant diseases.” Br J Nutr. Mar;83(Suppl 1): S157–163.
50 Of the many recent articles on this subject, see E. Södergren et al. 2001. “A diet containing rapeseed oil-based fats does not increase lipid peroxidation in humans when compared to a diet rich in saturated fatty acids.” Eur J Clin Nutr. Nov;55(11): 922–931.

Chapter 7
1 D. A. Drossman et al. 1993. “U.S. householder survey of functional gastrointestinal disorders. Prevalence, sociodemography, and health impact.” Dig Dis Sci. Sep;38(9): 1569–1580. According
to the American Gastroenterological Association (www.gastro.org/public/brochures/yourdigest.html),
“each month 44% of adults take antacids or other medicines” to treat a single gastrointestinal problem—heartburn.
2 Hypochlorhydria has often been misdiagnosed, either by doctors or by patients, because its symptoms, such as bloating, flatulence, and burning, resemble those of hyperchlorhydria (too much acid). As a result, some patients take antacids when they have the opposite problem. Many studies show that atrophic gastritis (little or no acid secretion in the stomach) is an increasing problem with age. As many as 20 to 30 percent of those over 60 in the U.S. have this condition. See, for example, S. D. Krasinski et al. 1986. “Fundic atrophic gastritis in an elderly population.” J Am Geriatr Soc. Nov;34(11): 800–806. Atrophic gastritis is a “predisposing factor for gastric cancer.” (M. Inoue et al. 2000. “Severity of chronic atrophic gastritis and subsequent gastric cancer occurrence.” Cancer Lett. Dec 8;161(1): 105–112.) Other problems associated with too little stomach acid include rheumatoid arthritis, anemia, coronary disease, asthma, anemia, and gallstones. See J. Wright and L. Lenard. 2001. Why Stomach Acid Is Good for You. New York: M. Evans & Co.
3 “In addition, 75% of adults worldwide are said to be lactose maldigesters or have low lactase levels.” “Lactose Maldigestion/Lactose Intolerance,” National Dairy Council (www.nationaldairycouncil.org/
lv104/nutrilib/calccounsel/06_ccr_rev.htm). “In Africa, Asia, and Latin America, prevalence rates range from 15–100%, depending on the population studied.” N. S. Scrimshaw and E. B. Murray. 1988. “The acceptability of milk and milk products in populations with a high prevalence of lactose intolerance.” Am J Clin Nutr. Oct;48(Suppl 4): 1079–1159. See also D. L. Swagerty Jr. et al. 2002. “Lactose intolerance.” Am Fam Physician. May 1;65(9): 1845–1850.
4 M. Morotomi and S. Kado. 2003. “Intestinal microflora and cancer prevention.” Gan To Kagaku Ryoho. Jun;30(6): 741–747; F. Guarner and J. R. Malagelada. 2003. “Gut flora in health and disease.” Lancet. May 24;361(9371): 1831.
5 Recent studies suggest that the cut and type of meat consumed may influence the risk for colon cancer. L. Ferguson. 2002. “Meat consumption, cancer risk and population groups within New Zealand.” Mut Res. Sep 30;506–507: 215–224; E. L. Matos and A. Brandani. 2002. “Review on meat consumption and cancer in South America.” Mut Res. Sep 30;506–507: 243–249.
6 One recent study found a reduction in cancer risk of 40 percent by doubling fiber intake from food. S. Bingham et al. 2003. “Dietary fibre in food and protection against colorectal cancer.” Lancet. May 3;361(9368): 1496–1501. These results contradict earlier research. “People in the top 20% who had the biggest reduction were eating far more fibre than in other studies which have not shown a relationship,” said S. Bingham, interviewed by P. Reaney for News in Science (www.abc.net.au/science/news). See also L. Ferguson and P. Harris. 2003. “The dietary fibre debate: more food for thought.” Lancet. May 3;361(9368): 1487–1488.
7 P. D’Adamo. 1997. Eat Right for Your Type. New York: G. P. Putnam’s & Sons.
8 For information about this test, see data from diagnostic laboratories, such as Great Smokies Diagnostic Laboratory (www.gsdl.com/assessments/cdsa) or Doctors’ Data Laboratory (www.doctorsdata.
com). See also a naturopathic text such as S. Barrie. 1999. “Comprehensive digestive stool analysis.” In M. T. Murray and J. E. Pizzorno. Textbook of Natural Medicine, 2nd ed. New York: Churchill Livingstone, pp. 107–116.
9 J. Bland. 1999. The 20-Day Rejuvenation Diet Program. New York: McGraw-Hill.
10 “Demonstration of the potential health benefits of short-chain fructooligosaccharides on colon cancer risk is an active field of research in animal and human nutrition,” according to F. R. Bornet and F. Brouns. “Immune-stimulating and gut health-promoting properties of short-chain fructo-oligosaccharides.” J Nutr Oct. 60(10 Pt 1): 326–334. See also C. Cherbut et al. 2003. “The prebiotic characteristics of fructooligosaccharides are necessary for reduction of TNBS-induced colitis in rats.” J Nutr. Jan;133(1): 21–27.
11 A. Ferrar. 2003. “Metal poisoning.” An Sist Sanit Navar. 26(Suppl 1): 141–153; L. Patrick. 2003. “Toxic metals and antioxidants.” Altern Med Rev. Apr;8(2): 106–128.
12 Antibodies are immunoglobulins (Ig). These are produced in response to an antigen, which is a substance the body perceives as a threat. IgG is one class of antibody, and it is normally present in the body at relatively high levels (10 mg/ml). IgG responses to food are typically delayed by as much as 48 hours and thus the symptoms, such as wheezing, bloating, loss of energy, and headaches, are often not associated with the triggering food. Most negative food reactions involve IgG.
13 IgE, like IgG, is a class of immunoglobulin. IgE is normally present in the body at low levels (0.5 µg/ml). With an IgE allergic reaction to a food, symptoms appear within seconds to a few hours. The IgE triggers cells that orchestrate immune responses, called mast cells, to start an inflammatory response. An extreme IgE allergic response can result in anaphylactic shock and death. For more information, see C. Janeway et al. 2001. “Allergy and hypersensitivity” in Immunobiology, 5th. ed. New York: Garland Publishing.
14 Toxoplasma gondii is a parasite prevalent in wild and domestic animals worldwide. According to an expert at the National Institute of Allergy and Infectious Diseases (NIAID), “Many parasitic diseases such as giardiasis and cryptosporidiosis are not always reported to health authorities, so that we suspect that the extent and impact of parasitic diseases in the United States is underestimated.” In addition, “up to three million women have acquired sexually transmitted T. vaginalis.” News from NIAID, November 1, 1993 (www.aegis.com/news/niaid/1993/CDC93081.html).
15 D. Karsenti et al. 2001. “Small intestine bacterial overgrowth: six case reports and literature review.” Rev Med Interne. Jan;22(1): 20–29; S. M. Riordan et al. 2001. “Small intestinal bacterial overgrowth and the irritable bowel syndrome.” Am J Gastroenterol. Aug;96(8): 2506–2508.
16 “Helicobacter pylori infection is one of the most common in man,” according to S. A. Dowsett and M. J. Kowolik. 2003. “Oral Helicobacter pylori: can we stomach it?” Crit Rev Oral Biol Med. 14(3): 226–233.
17 A. Gewirtz et al. 2002. “Intestinal epithelial pathobiology: past, present, and future.” Best Practice & Res Clin Gastroenterol. Dec;16(6): 851–867; D. Hollander. 1999. “Intestinal permeability, leaky gut, and intestinal disorders.” Curr Gastroenterol Rep. Oct;1(5): 410–416.
18 “The word ‘auto’ is the Greek word for self. The immune system is a complicated network of cells and cell components (called molecules) that normally work to defend the body and eliminate infections caused by bacteria, viruses, and other invading microbes. If a person has an autoimmune disease, the immune system mistakenly attacks self, targeting the cells, tissues, and organs of a person’s own body. A collection of immune system cells and molecules at a target site is broadly referred to as inflammation.” Understanding Autoimmune Diseases, National Institute of Allergy and Infectious Diseases; www.niaid.nih.gov/publications/autoimmune.htm.
19 See note 17, above.
20 S. Holt, ed. 2000. Natural Ways to Digestive Health: Interfaces Between Conventional and Alternative Medicine. New York: M. Evans and Company.
21 Y. Ringel et al. 2001. “Irritable bowel syndrome.” Annu Rev Med. 52: 319–338; C. M. Porth. 1998. “Irritable bowel syndrome.” In Pathophysiology: Concepts of Altered Health States, 5th ed. Philadelphia: Lippincott, pp. 729–730.
22 A. R. Gaby. 2003. “Treatment with enteric-coated peppermint oil reduced small-intestinal bacterial overgrowth in a patient with irritable bowel syndrome.” Altern Med Rev. Feb;8(1):3; R. M. Kline et al. 2001. “Enteric-coated, pH-dependent peppermint oil capsules for the treatment of irritable bowel syndrome in children.” J Pediatr. Jan;138(1): 125–128.
23 Produced by Proper Nutrition; www.propernutrition.com.
24 See A. Picard. “Today’s fruits, vegetables lack yesterday’s nutrition.” Globe and Mail, July 6, 2002; www.globeandmail.com/special/food/wxfood.html.
25 Pesticides are classified when they are registered on the basis of animal and epidemiological tests. See www.epa.gov/pesticides/health/tox_categories.htm.
26 The extoxnet is a good source of information on these agricultural chemicals. It is a pesticide information project of the Cooperative Extension Offices of Cornell University, Michigan State University, Oregon State University, and University of California at Davis. For terbutryn, see http://pmep.cce.cornell.edu/
profiles/extoxnet/pyrethrins-ziram/terbutryn-ext.html. Also see the index of cleared science reviews under the Freedom of Information Act; www.epa.gov/pesticides/foia/reviews/080813.htm.
27 I. Kimber and R. J. Dearman. 2002. “Factors affecting the development of food allergy.” Proc Nutr Soc. Nov;61(4): 435–439; E. Fernandez et al. 2000. “Diet diversity and colorectal cancer.” Prev Med. Jul;31(1): 11–14.
28 M. Zimmerman. 2001. Eat Your Colors: Maximize Your Health by Eating the Right Foods for Your Body Type. New York: Henry Holt & Co.
29 K. Mukamal et al. 2002. “Tea consumption and mortality after acute myocardial infarction.” Circulation. May 6;105: 2476.
30 Green tea contains a high level of catechins, which are a type of polyphenol. Polyphenols are antioxidants. The catechins in black tea are lost during processing. J. D. Lambert and C. S. Yang. 2003. “Cancer chemopreventative activity and bioavailability of tea and tea polyphenols.” Mutat Res. Feb–Mar;523–524: 201–208; K. Maeda et al. 2003. “Green tea catechins inhibit the cultured smooth muscle cell invasion through the basement barrier.” Atherosclerosis. Jan;166(1): 23–30.
31 A. Sierksma et al. 2002. “Moderate alcohol consumption reduces plasma C-reactive protein and fibrinogen levels; a randomized, diet-controlled intervention study.” Eur J Clin Nutr. Nov;56(11): 1130–1136.
32 Atkins for Life: The Complete Controlled Carb Program for Permanent Weight Loss and Good Health and Dr. Atkins’ Age-Defying Diet.
33 WHO. 2002. FAO/WHO Consultation on the Health Implications of Acrylamide in Food. Summary report of a meeting held in Geneva, 25–27 June 2002 (available at www.who.int/fsf/). Also see “Acrylamide in food.” European Commission, Scientific Committee on Food; http://europa.eu.int/
comm/food/fs/sfp/fcr/acrylamide/acryl_index_en.html. FDA Action Plan for Acrylamide in Food, March 2004, FDA/Center for Food Safety & Applied Nutrition, www.cfsan.fda.gov/~dms/acrypla3.html; Exploratory Data on Acrylamide in Food, March 2003, FDA/Center for Food Safety & Applied Nutrition, www.cfsan.fda.gov/~dms/acrydata.html; Exploratory Data on Acrylamide in Food, March 2004, FY 2003 Total Diet Study Results, FDA/Center for Food Safety & Applied Nutrition, www.cfsan.fda.gov/
~dms/acrydat2.html.
34 Eat More, Weigh Less: Dr. Dean Ornish’s Life Choice Program for Losing Weight Safely While Eating Abundantly and Everyday Cooking with Dr. Dean Ornish: 150 Easy, Low-Fat, High Flavor Recipes.
35 Information about the USDA food pyramid is available at www.nal.usda.gov/fnic/
Fpyr/pyramid.html and www.nal.usda.gov:8001/py/pmap.htm.
36 See W. Willett. 2001. Eat, Drink, and Be Healthy. New York: Simon & Schuster. Also see “Food pyramids.” Harvard School of Public Health; www.hsph.harvard.edu/nutritionsource/pyramids.html.

Chapter 8
1 According to this study’s results, a woman who is obese at age 20 can expect a reduction in life expectancy of 8 years, while an obese 20-year-old man can anticipate a loss of 13 years compared to the life span of his normal-weight peers. When weight gain does not occur until later in life, the results are still significant, though not as dramatic. Merely being overweight (not obese) at age 40 shortens average life span by 3.1 years. People who are overweight and smoke can anticipate living 7 years less. The loss of life consequent to being overweight is about equal to that from cigarette smoking. K. R. Fontaine et al. 2003. “Years of life lost due to obesity.” JAMA. Jan 8;289(2): 187–193.
2 T. E. Strandberg et al. 2003. “Impact of midlife weight change on mortality and quality of life in old age.” Int J Obes. Aug;27(8): 950–954; S. A. French et al. 1997. “Weight variability and incident disease in older women: the Iowa Women’s Health Study.” Int J Obes. Mar;21(3): 217–223.
3 A. H. Mokdad et al. “Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001.” JAMA. Jan 1;289(1): 76–79; National Institutes of Health. 1998. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults. Bethesda, Maryland: Department of Health and Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute, pp. 12–20; “Overweight and obesity: health consequences.” The Surgeon General’s Call to Action; www.surgeongeneral.
gov/topics/obesity/calltoaction/fact_consequences.htm.
4 “After adjustment for established risk factors, there was an increase in the risk of heart failure of 5 percent for men and 7 percent for women for each increment of 1 in BMI,” per S. Kenchaiah et al. 2002. “Obesity and the risk of heart failure.” N Engl J Med. Aug 1;347(5): 305–313; F. W. Ashley Jr. and W. B. Kannell. 1974. “Relation of weight change to changes in atherogenic traits: the Framingham Study.” J Chronic Dis. Mar.;27(3): 103–114.
5 According to a recent Centers for Disease Control and Prevention (CDC) survey, “more than two-thirds of Americans—64 percent of men and 78 percent of women—are either dieting to lose weight or watching what they eat,” as reported in “Many Americans fed up with diet advice,” New York Times, January 2, 2001. Yet currently “more than 60 million Americans (a third of the population) are overweight,” per the CDC. “The link between physical activity and morbidity and mortality,” National Center for Chronic Disease Prevention and Health Promotion; www.cdc.gov/nccdphp/sgr/mm.htm.
6 S. Orenstein. “The pill that will make you thin.” Business 2.0, March 2004, pp. 108–115.
7 G. K. Goodrick and J. P. Foreyt. 1991. “Why treatments for obesity don’t last.” J Am Diet Assoc. Oct; 91(10): 1243–1247; F. M. Kramer et al. 1989. “Long-term follow-up of behavioral treatment for obesity: patterns of weight regain among men and women.” Int J Obes. 13(2): 123–136.
8 M. Hendricks. 2003. “Off the scale.” Johns Hopkins Public Health: The Magazine of the Johns Hopkins Bloomberg School of Public Health, Spring; K. D. Brownell. 1989. “Weight cycling,” Am J Clin Nutr. May;49(Suppl 5): 937; G. L. Blackburn et al. 1989. “Weight cycling: the experience of human dieters.” Am J Clin Nutr. May;49(Suppl 5): 1105–1109.
9 Each pound of fat stores about 3,500 calories.
10 Weights at ages 25–59 based on lowest mortality. Weight in pounds according to frame (wearing indoor clothing weighing 3 lbs. and shoes with 1-in. heels). Courtesy of Metropolitan Life Insurance Company.
11 A number of recent studies are exploring the relationship between body mass index (BMI) and the percentage of body fat (%BF) as a means of developing health guidelines. See, for example, U. G. Kyle et al. 2003. “Body composition interpretation: Contributions of the fat-free mass index and the body fat mass index.” Nutrition. Jul–Aug;19(7–8): 597–604; D. Gallagher et al. 2000. “Healthy percentage body fat ranges: an approach for developing guidelines based on body mass index.” Am J Clin Nutr. Sep;72(3): 694–701. Age and race have both been cited as factors to consider in setting the normal ranges for %BF. The onset of puberty is linked to the development of energy storage in the form of fat. See, for example, B. Vizmanos and C. Martí-Henneberg. 2000. “Puberty begins with a characteristic subcutaneous body fat mass in each sex.” Eur J Clin Nutr. Mar;54(3): 203–208.
12 S. P. Weisberg and A. W. Ferrante Jr. 2003. “Obesity is associated with macrophage accumulation in adipose tissue.” Journal of Clinical Investigation. Dec 15;112: 1796–1808. Available at www.jci.org/cgi/content/full/112/12/1796; K. E. Wellen and G. S. Hotamisligil. 2003. “Obesity-induced inflammatory changes in adipose tissue.” Journal of Clinical Investigation. Dec 15;112: 1785–1788. Available at www.jci.org/cgi/content/full/112/12/1785; H. Xu and H. Chen. 2003. “Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance.” Journal of Clinical Investigation Dec 15;112: 1821–1830. Available at www.jci.org/cgi/content/full/112/12/1821; G. S. Hotamisligil et al. 1994. “Tumor necrosis factor alpha inhibits signaling from the insulin receptor.” Proceedings of the National Academy of Sciences May 24;91: 4854–4858. Available at www.pnas.org/cgi/reprint/91/11/4854.
13 D. V. Schapira et al. 1991. “Upper-body fat distribution and endometrial cancer risk,” JAMA. Oct 2;266(13): 1808–1811.
14 The link between abdominal obesity and health issues such as diabetes and metabolic syndrome has been made in many different populations around the globe. See, for example, N. K. Vikram et al. 2003. “Anthropometry and body composition in northern Asian Indian patients with type 2 diabetes.” Diabetes Nutr Metab. Feb;16(1): 32–40; J. A. Lawati et al. “Prevalence of the metabolic syndrome among omani adults.” Diabetes Care. Jun;26(6): 1781–1785. There is a “modest relationship” between abdominal obesity and coronary heart disease, according to K. M. Rexrode et al. 2001. “Abdominal and total adiposity and risk of coronary heart disease in men.” Int J Obes. Jul;25(7): 1047–1056.
15 In the Nurses’ Health Study II, “most women who lost a clinically significant amount of weight regained it, [however,] they gained less weight over the entire 6 year period than their peers,” per A. E. Field et al. 2001. “Relationship of a large weight loss to long-term weight change among young and middle-aged U.S. women.” Int J Obes. Aug;25(8): 1113–1121. Some recent results are encouraging: “A large proportion of the American population has lost 5 10% of their maximum weight and has maintained this weight for at least 1 year.” M. T. McGuire et al. 1999. “The prevalence of weight loss maintenance among American adults.” Int J. Obes. Dec;23(22): 1314–1319.
16 D. E. Cummings et al. 2002. “Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery.” N Engl J Med. May 23;346(21): 1623–1630. See also D. E. Cummings and M. W. Schwartz. 2003. “Genetics and pathophysiology of human obesity.” Annu Rev Med. 54: 453–471.
17 The more muscle you have, the more calories you burn, even while resting. Many fitness trainers recommend weight training to build muscle mass. See, for example, R. Roubenoff et al. 2000. “The effect of gender and body composition method on the apparent decline in lean mass-adjusted resting metabolic rate with age.” J Gerontol A Biol Sci Med Sci. Dec;55(12): M757–760. There may also be “metabolic demands of resynthesizing glycogen and repairing tissue damage,” per R. Andersen. 1999. “Exercise, an active lifestyle, and obesity.” Phys Sportmed. Oct 1;27(10).
18 “Energy can be expended by performing work or producing heat (thermogenesis). Adaptive thermogenesis, or the regulated production of heat, is influenced by environmental temperature and diet. Mitochondria, the organelles that convert food to carbon dioxide, water and DP, are fundamental in mediating effects on energy dissipation.” B. B. Lowell and B. M. Spiegelman. 2000. “Towards a molecular understanding of adaptive thermogenesis.” Nature. 404: 652–660.
C. R. Kahn points out that exercise represents only 10-20 percent of energy expenditure in most people, with the rest “represented by the basal metabolic rate and thermogenesis.” He claims that in mammals, at least 20 percent of the thermogenesis “is due to an ‘energy leak’ that occurs through movement of protons across the mitochondrial inner membrane of cells.” “Triclycerides and toggling the tummy.” 2000. Nature Genetics. 25(1): 6–7.
19 S. D. Hursting et al. 2003. “Calorie restriction, aging, and cancer prevention: mechanisms of action and applicability to humans.” Annu Rev Med. 54: 131–152; V.E. Archer. 2003. “Does dietary sugar and fat influence longevity?” Med Hypotheses. Jun;60(6): 924–929.
20 “The effect of caloric restriction (CR) on lifespan has been reported in nearly all [short-lived] species tested and has been reproduced hundreds of times under a variety of different laboratory conditions. In addition to prolonging lifespan, CR also prevents or delays the onset of age-related disease and maintains many physiological functions at more youthful levels . . . The studies on nonhuman primates are . . . suggesting that the effect of CR on aging is universal across species.” M. A. Lane et al. 2002. “Caloric restriction and aging in primates: relevance to humans and possible CR mimetics.” Microsc Res Tech. Nov 15;59(4): 335–338.
21 B. P. Yu et al. 1982. “Life span study of SPF Fischer 344 male rats fed ad libitum or restricted diets: longevity, growth, lean body mass, and disease,” J Gerontol. Mar;37(2): 130–141.
22 Y. Minokoshi et al. “AMP-Kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus,” Nature online, March 17, 2004.
23 S. G. Bouret, S. J. Draper, and R. B. Simerly. 2004. “Trophic Action of Leptin on Hypothalamic Neurons that Regulate Feeding,” Science. April 2;304.
24 N. Angier. “Diet offers tantalizing clues to a long life.” New York Times, April 17, 1990, sec. C.
25 Caloric restriction has been shown to inhibit the growth of spontaneous, transplanted, or chemically induced tumors in rats and mice. At 40 percent caloric restriction, growth of chemically induced breast and colon tumors was significantly inhibited. Exercise has also been shown to inhibit tumor growth. Sedentary rats who were allowed to eat freely had 108 percent higher incidence of induced colon tumors than free-eating rats subjected to vigorous treadmill exercise. D. Kritchevsky. 1990. “Influence of caloric restriction and exercise on tumorigenesis in rats,” Proc Soc Exp Biol Med. Jan;193(1): 35–38.
26 N. Angier. See note 24, above.
27 M. Blüher, B. B. Kahn, and C. R. Kahn. 2003. “Extended longevity in mice lacking the insulin receptor in adipose tissue.” Science. Jan 24;299(5606): 572–574; M. Blüher et al. 2002. “Adipose tissue selective insulin receptor knockout protects against obesity and obesity-related glucose intolerance.” Dev Cell. Jul;3(1): 25–38.
28 A. Cerami. 1985. “Hypothesis: glucose as a mediator of aging.” J Am Geriatr Soc. Sep;33 (9): 626–634; E. J. Masoro et al. “Evidence for the glycation hypothesis of aging from the food-restricted rodent model.” J Gerontol. Jan;44(1): B20–22.
29 C. K. Ferrari and E. A. Torres. 2003. “Biochemical pharmacology of functional foods and prevention of chronic diseases of aging.” Biomed Pharmacother. Jul;57(5–6): 251–260; D. T. Chiu and T. Z. Liu. 1997. “Free radical and oxidative damage in human blood cells.” J Biomed Sci. 4(5): 256–259.
30 A. Koizumi et al. 1987. “Influences of dietary restriction and age on liver enzyme activities and lipid peroxidation in mice.” J Nutr. Feb;117(2): 361–367.
31 R. Licastro, R. Weindruch, and R. L. Walford. 1986. “Dietary restriction retards the age-related decline of DNA repair capacity in mouse splenocytes,” in Topics in Aging Research in Europe 9. A. Facchini, J. J. Haaijman, and G. Labo, eds. Rijswijk: EURAGE, pp. 53–61; R. J. Tice and R. B. Setlow. 1985. “DNA repair and replication in aging organisms and cells,” in Handbook of the Biology of Aging. C. E. Finch and E. L. Schneider, eds. New York: Van Nostrand Reinhold, pp. 173–224.
32 C. Kahn. 1990. “His theory is simple: eat less, live longer. A lot longer.” Longevity. Oct: 61–66, esp. 64.
33 N. Angier. See note 24 on page 400.
34 “Caloric Restriction without the Restriction” is a registered trademark of Ray & Terry’s Longevity Products.
35 Joslin Diabetes Center press release, January 2004, “Study shows it may someday be possible to stay slim,” www.joslin.harvard.edu/news/FirkoMouseStudy01.shtml. The study was published in Science: M. Blüher, B. Kahn, and C. R. Kahn. 2003. “Extended longevity in mice lacking the insulin receptor in adipose tissue.” Jan 24;299(5606): 572–574.
36 Precose is recommended by the Joslin Diabetes Center as “one of six types of diabetes pills currently available to treat type 2 diabetes.” www.joslin.harvard.edu/education/library/precose.shtml.
37 Xenical is produced by Roche Pharmaceuticals (www.rocheusa.com/products/xenical/). A number of recent studies have supported the effectiveness of Xenical (orlistat). See, for example, S. A. Harrison et al. 2003. “Orlistat in the treatment of NASH: a case series.” Am J Gastroenterol. Apr;98(4): 926–930; M. Hanefeld and G. Sachse. 2002. “The effects of orlistat on body weight and glycemic control in overweight patients with type 2 diabetes: a randomized, placebo controlled trial.” Diabetes Obes Metab. Nov;4(6): 415–423.
38 M. D. Gades and J. S. Stern. 2003. “Chitosan supplementation and fecal fat excretion in men.” Obes Res. May;11(5): 683–688.

Chapter 9
1 U.S. Department of Agriculture, Agriculture Factbook 2001–2002, chapter 2, “Profiling food consumption in America,” www.usda.gov/factbook/chapter2.htm. This 152-pound figure represents the amount of sugar available wholesale. USDA recommends that “an average person on a 2,000-calorie daily diet” consume no more than 20 teaspoons of sugar per day. The average annual consumption of 152 pounds of sweeteners is equivalent to 52 teaspoonfuls of added sugar per day. Though approximately 20 teaspoonfuls are lost or wasted, Americans are still consuming at least double the recommended amount of
sugar. The percentage increase is also alarming, increasing by almost 40 percent between 1960 and 2000 (for a chart of the increase since 1983, see www.cspinet.org/reports/sugar/sugarconsumption.html). “Consumption has risen every year but once since 1983” (www.cspinet.org/new/sugar_limit.html).
In addition, see USDA, Agricultural Outlook March 1997, “U.S. sugar consumption continues to grow,” www.ers.usda.gov/publications/agoutlook/mar1997/ao238g.pdf.
2 www.nsda.org/softdrinks/History/funfacts.html. Estimates vary on the percentage of sugar consumed in soft drinks, but they account for between 22 percent (Agriculture Factbook, see En. 1) and 33 percent (www.cspinet.org/reports/sugar/sugarorigin.html) of Americans’ sugar intake. According to a USDA researcher, soft drinks are the prime culprit in the diet of high consumers of sugar (www.cspinet.org/
new/sugar_limit.html).
3 See the WHO Technical Report # 916. 2003. “Diet, Nutrition and the Prevention of Chronic Diseases” available at www.who.int/hpr/NPH/docs/who_fao_expert_report.pdf.
4 As quoted in O. Dwyer. 2004. “U.S. government rejects WHO’s attempts to improve diet.” BMJ. Jan 24;328(7433): 185.
5 The U.S. Dept. of Health and Human Services issued a report largely condemning the findings of the WHO Technical Report #916 “Diet, Nutrition and the Prevention of Chronic Diseases” on Jan. 4, 2004, stating their beliefs that there was little proven connection between obesity and consumption of fast food or high glycemic foods. See www.commercialalert.org/bushadmincomment.pdf.
6 American Academy of Pediatrics Committee on School Health. 2004. “Soft drinks in schools.” Pediatrics. Jan;113(1 Pt 1): 152–154.
7 Dr. Banting was joined in his research by a medical student working with him at the University of Toronto, Mr. C. H. Best. The discovery of insulin by two young unheralded researchers is “one of medicine’s great success stories” (www.aventis.com/future/downloads/PDF/fut0203/En_03_2002_the_
discovery_of_insulin.pdf). See also F. G. Banting et al. 1991. “Pancreatic extracts in the treatment of diabetes mellitus: preliminary report. 1922.” CMAJ. Nov 15;145(10): 1281–1286.
8 According to the National Center for Health Statistics, in 2000, 64.5 percent of Americans were overweight and 30.5 percent were obese. K. M. Flegel et al. 2002. “Prevalence and trends in obesity among U.S. adults, 1999–2000.” JAMA. Oct 9;288(14): 1723–1727.
9 Ten years ago, “only” one out of two adults was overweight and one in five obese. Talk about a growth industry! J. E. Manson and S. S. Bassuk. 2003. “Obesity in the United States: a fresh look at its high toll.” JAMA. Jan 8;289(2): 229–230.
10 K. R. Fontaine et al. 2003. “Years of life lost due to obesity.” JAMA. Jan 8;289(2): 187–193.
11 E. S. Ford, W. H. Giles, and W. H. Dietz. 2002. “Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey.” JAMA. Jan 16;287(3): 356–359.
12 A. Agatston. 2003. The South Beach Diet. Emmaus, Pennsylvania: Rodale, p. 76.
13 Reaven initially called it “metabolic syndrome,” see G. M. Reaven. 1988. “Banting Lecture: Role of insulin resistance in human disease.” Diabetes. 37: 1595–1607. As of October 2003, according to the ICD-9-CM (International Classification of Diseases), it should now be called “dysmetabolic syndrome X” or “dysmetabolic syndrome,” but because “metabolic syndrome” is more commonly known and used, we will continue to use the older nomenclature.
14 Executive Summary of the 3rd Report of the U.S. National Cholesterol Education Program (NCEP)—Adult Treatment Panel III (ATP III); www.nhlbi.nih.gov/guidelines/cholesterol/profmats.htm.
15 If people are taking antihypertensives or antidiabetic drugs, they are counted as if they had a high blood pressure or an elevated fasting blood glucose.
16 G. M. Reaven et al. 1993. “Insulin resistance and hyperinsulinemia in individuals with small dense LDL particles.” J Clin Invest. 92: 141-146.
17 Ford, Giles, and Dietz, op cit.
18 The other 80 percent are able to compensate at least temporarily by increased pancreatic insulin production, creating a long-standing state of elevated insulin levels. L. C. Jones and A. Clark. 2001. “Beta cell neogenesis in type 2 diabetes mellitus.” Diabetes. 50(Suppl 1): S186–187.
19 J. L. Wautier and P. J. Guillausseau. 2001. “Advanced glycation end products, their receptors and diabetic angiopathy.” Diabetes Metab. Nov;27(5 Pt 1): 535–542.
20 C. Netzer. 2000. The Complete Book of Food Counts. New York: Random House.
21 News release, 2003. “Type 2 diabetes linked to a family of metabolic genes,” Joslin Diabetes Center, July, at www.joslin.org/news/GenesType2.shtml.
22 C. Chen et al. 2003. Nature Biotechnology. 21: 294–301.
23 J. M. Lehman et al. 1995. “An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma).” J Biol Chem. Jun 2;270(22): 12953–12956.
24 A. M. J. 2003. “Clinical islet transplant: current and future directions towards tolerance.” Immun Reviews. 196: 219–236.
25 “Growing human organs on the farm.” NewScientist. 180(2426): 4.
26 News release. “Joslin Comments on Diabetes Study Published in Science on Nov. 14, 2003”; www.joslin.org/news/ScienceReport1103.shtml.
27 V. K. Ramiya. 2000. “Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells.” Ann NY Acad Science. May; 958: 59–68.
28 L. Knapp. “Diagnosis and medicine in a pill.” Wired News, July 28, 2003.
29 S. Vasan, P. Foiles, and H. Founds. 2003. “Therapeutic potential of breakers of advanced glycation end product-protein crosslinks.” Arch Biochem Biophys. Nov 1;419(1): 89–96; D. A. Kass. 2003. “Getting better without AGE: new insights into the diabetic heart.” Circ Res. Apr 18;92(7): 704–706.
30 D. A. Kass et al. 2001. “Improved arterial compliance by a novel advanced glycation end-product crosslink breaker.” Circulation. Sep 25;104(13): 1464–70.
31 J. P. Despres et al. 1996. “Hyperinsulinemia as an independent risk factor for ischemic heart disease.” N Engl J Med. Apr 11;334(15): 952–957.
32 In many centers, even the venerable glucose tolerance test has been abandoned in favor of the more streamlined “hemoglobin A1c,” an excellent test to monitor diabetes, but completely inadequate to detect prediabetics or people with a tendency to TMS.
33 Early in the course of type 2 diabetes, insulin levels often remain elevated. Later on, after years of excess insulin production (and gradual replacement of insulin-producing cells with amyloid), the pancreas can “burn out” and insulin levels can fall to “normal” or low levels.
34 See, for example, G. S. Watson and S. Craft. 2003. “The role of insulin resistance in the pathogenesis of Alzheimer’s disease: implications for treatment.” CNS Drugs. 17(1): 27–45. Coronary artery disease is also linked to insulin resistance: “The development of insulin resistance is considered to be a pivotal event in vascular risk” (P. J. Grant. 2003. “The genetics of atherothrombotic disorders: a clinician’s view.” J Thromb Haemost. Jul;1(7): 1381–1390). Yet a third disease linked to insulin resistance is fatty liver disease; both the prevalence and severity of the disease are linked to body mass index and waist circumference. (A. J. Scheen and F. H. Luyckx. 2003). “Nonalcoholic steatohepatitis and insulin resistance.” Acta Clin Belg. Mar–Apr;58(2): 81–91.)
Insulin resistance is also linked to non-age-related problems such as pregnancy-induced hypertension (E. W. Seely and C. G. Solomon. 2003. “Insulin resistance and its potential role in pregnancy-induced hypertension.” J Clin Endocrinol Metab. Jun;88(6): 2393–2398).
35 F. S. Facchini et al. 2001. “Insulin resistance as a predictor of age-related diseases.” J Clin Endocrinol Metab. Aug;86(8): 3574–3578.
36 R. A. Freitas Jr. 1999. Nanomedicine, Volume 1: Basic Capabilities. Austin, Texas: Landes Bioscience, pp. 93–122.
37 www.bizjournals.com/columbus/stories/2000/09/25/story2.html?page52.
38 Medtronic news release, “Research Presented at ADA Annual Meeting Demonstrates Accuracy and Feasibility of Artificial Pancreas Components,” at www.medtronic.com/newsroom/news_20020617b.html.
39 S. Jacob et al. 1999. “Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial.” Free Radic Bio Med. 27(3–4): 309–314.
40 G. Boden et al. 1996. “Effects of vanadyl sulfate on carbohydrate and lipid metabolism in patients with non-insulin-dependent diabetes mellitus.” Metabolism. Sep;45(9): 1130–1135.
41 L. H. Storlien et al. 1987. “Fish oil prevents insulin resistance induced by high-fat feeding in rats.” Science. 237(4817): 885–888.
42 R. B. Singh et al. 1999. “Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance in hypertensive patients with coronary artery disease.” J Hum Hypertens. 13: 203–208.
43 M. F. McCarty. 1999. “High-dose biotin, an inducer of glucokinase expression may synergize with chromium picolinate to enable a definitive nutritional therapy for type II diabetes.” Med Hypotheses. 52(5): 401–406.
44 P. M. Piatti et al. 2001. “Long-term oral L-arginine administration improves peripheral and hepatic insulin sensitivity in type 2 diabetic patients.” Diabetes Care. 24(5): 875–880.
45 C. W. Bates. 1995. “DHEA attenuates study-induced declines in insulin sensitivity in postmenopausal women.” Ann NY Acad Sci. 774: 291–293.
46 W. Dean. “Metformin: The Most Effective Life Extension Drug Is Also a Safe, Effective Weight Loss Drug” on www.antiaging-systems.com/extract/metforminweight.htm.
47 E. L. Barrett-Connor. 1995. “Testosterone and risk factors for cardiovascular disease in men.” Diab Metab. 21: 156–161.

Chapter 10
1 The test for “biological age,” called the H scan test, includes tests for auditory reaction time, highest audible pitch, vibrotactile sensitivity, visual reaction time, muscle movement time, lung (forced expiratory volume), visual reaction time with decision, muscle movement time with decision, memory (length of sequence), alternative button tapping time, and visual accommodation.
2 G. S. Rothfeld, S. Levert. 2001. The Acupuncture Response. New York: Contemporary Books.

Chapters: 1-5, 11-15, 16-20, 21-23