"the adverse cardiovascular...": Susic et al. 2004.

"Current evidence points...": Peppa et al. 2003.

CHAPTER TWELVE:.

SUGAR.

Epigraph. "M. Delacroix...": Bril at-Savarin 1986:104.

Reaven initiated study of glycemic index: c.r.a.po et al. 1977 ("traditional y held tenet..."). Reaven more interested in insulin: Interview, Gerald Reaven.

Jenkins and Wolever's research: Jenkins et al. 1981. "tremendous": Interview, Thomas Wolever.

Vitriolic debate: Interviews, Gerald Reaven ("Ice cream has..."), David Jenkins, and Thomas Wolever. See also Coulston and Reaven 1997 and the response, Wolever 1997.

Fructose and the glycemic index: Mayes 1993.

"We see no reason...": Bantle et al. 1983. Official government position: Glinsmann et al. 1986:s6566. "sucrose or sucrose-containing foods...": ADA 2006.

"no conclusive evidence...": Glinsmann et al. 1986:s15.

Surgeon General's Report: USDHHS 1988:111. Diet and Health: NRC 1989:9.

HFCS and climbing sugar consumption: Putnam et al. 2002:8.

Sugar and starch consumption over the twentieth century: USDA 2000; Putnam et al. 2002. Sugar as dietary nuisance: See, for instance, Mayer 1976.

Fructose content of fruit: "Sweetener" entry, Encyclopaedia Brittanica. Fructose perceived as healthy: See, for instance, Brody 1983b; Donohue 1988.

Metabolism of glucose and fructose: Shafrir 1991. "const.i.tutes a metabolic load...": Interview, Eleazar Shafrir. Footnote. Higgins 1916.

"In the 1980s...": Interview, Judith Hal frisch. Sugar raises cholesterol: Swanson et al. 1992. For unbiased reviews of metabolic effects of fructose, see Hol enbeck 1993; IOM 2002:297303.

"pattern of fructose metabolism": Mayes 1993. Fructose causes insulin resistance: Shafrir 1985. Reiser observed in humans: Reiser et al. 1981.

Fructose-induced hypertension: See Hodges and Rebel o 1983; Hw.a.n.g et al. 1987.

"This is real y the harmful...": Interview, Peter Mayes.

Fructose and AGEs: Bunn and Higgins 1981; Dil s 1983. Ten times more effective: McPherson et al. 1988; Suarez et al. 1989. More resistant AGEs: Suarez et al. 1995. Increases LDL oxidation: Mowri et al. 2000.

The COMA report: U.K. Department of Health 1989:43.

"The panel concluded...": Ibid.

Dedicated an entire issue: ACJN, November 1993. "Further studies...": Tappy and Jequier 1993.

Inst.i.tute of Medicine spent twenty pages: IOM 2002:295324 ("insufficient evidence," 323; no reason to pursue research, 32324).

Half a dozen research projects: NIH CRISP database search, keywords "fructose" and "sucrose." 203 "no conclusive evidence...": Glinsmann et al.

1986:s6566.

CHAPTER THIRTEEN:.

DEMENTIA, CANCER, AND AGING.

Epigraph. "The bottom line...": Tanzi and Parson 2000:201.

NIH funding of Alzheimer's research 1970s and 1980s: NIH CRISP database search, keywords "Alzheimer's" and "dementia." 205 Apo E4 and Alzheimer's: Strittmatter et al. 1993. Alzheimer's researchers blame cholesterol and saturated fat: See, for instance, Mattson 2004. Footnote. See, for instance, Marx 2001 ("link between").

j.a.panese Americans vs. j.a.panese: Graves et al. 1996. African Americans vs. rural Africans: Hendrie et al. 2001.

Studies in large populations: Ott et al. 1999 (Rotterdam: "direct or indirect"); Leibson et al. 1997 (Minnesota); Luchsinger et al. 2001 (Manhattan); Arvanitakis et al. 2004 (Midwest); Peila et al. 2002 (Honolulu). Hyperinsulinemia and metabolic syndrome: Kuusisto et al. 1997; Vanhanen et al. 2006.

Confusion of Alzheimer's with vascular dementia: See Kalaria 2002; Zekry et al. 2002; Korczyn 2002.

Snowdon's nun study: Snowdon 2003.

Acc.u.mulation of vascular dementia accelerates Alzheimer's: See, for instance, Ravona-Springer et al. 2003.

Amyloid precursor protein exists natural y: Interview, Rudolph Tanzi.

AGEs in plaques and tangles: Yan et al. 1994; Smith et al. 1994; Vitek et al. 1994. In immature plaques: Sasaki et al. 1998.

The AGEs-Alzheimer's hypothesis: Grossman 2003; Obrenovich and Monnier 2004; Moreira et al. 2005.

Involvement of insulin: Qiu et al. 1998.

Animal experiments: Farris et al. 2003; Mil er et al. 2003; Farris et al. 2004. Footnote. Kim et al. 2007.

Boosting insulin enhances memory: Craft et al. 1996. In 2003, Craft reported: Watson et al. 2003. "We're not saying...": Interview, Suzanne Craft.

Selkoe and Tanzi on "attendant therapeutic implications...": Farris et al. 2004.

Higginson's studies of cancer incidence: Reviewed in Higginson 1981; Higginson 1997. "It would seem, therefore...": Quoted in Dol and Peto 1981:1197.

At least 75 to 80 percent: Dol and Peto 1981:125660.

Role of man-made chemicals minimal, diet maximal: Ibid.:1256 (table 20).

"extrinsic" and "environmental factors": See Maugh 1979 and Dol and Peto 1981:1197. "carcinogenic soup": Greenberg 1979. "It appears that...": Higginson 1983. Geneva vs. Birmingham, Sweden vs. j.a.pan: Maugh 1979. Footnote. Quoted in Maugh 1979.

Cold Spring Harbor talks: Hiatt et al. 1977:605956.

"gross aspects..." and "ingestion of traces...": Dol and Peto 1981:1258. Cancer in Seventh-day Adventists: Phil ips 1975.

Cancer in Mormons: Lyon and Sorenson 1978; Lyon et al. 1980. "among the biggest...": Dol and Armstrong 1981:103. For the next twenty years: See, for instance, Wynder et al. 1983; Carrol and Kritchevsky 1993; U.K. Department of Health 1998.

Failed to identify diet-related carcinogens: Interviews, W. Robert Bruce, Richard Dol and Robert Weinberg. Cancer epidemiologists made little attempt: See, for instance, World Cancer Research Fund and American Inst.i.tute for Cancer Research 1997: 50919; U.K. Department of Health 1998:189207.

Cleave had suggested: Cleave 1975:2838. Yudkin on five nations: Yudkin 1986:137. Diet and Health on carbohydrates: NRC 1989:28283.

"strikingly similar": Giovanucci 2001.

Rous's semi-starvation research: Rous 1914. McCay reported: McCay et al. 1935. Tannenbaum's research: Reviewed in Tannenbaum 1959 ("many types of tumors...," 530; "pathologic changes...," 523).

Hormone-dependent factors linked to cancers: Armstrong 1977. Increase in cancer incidence with weight gain: Dol and Peto 1981:1234; World Cancer Research Fund and American Inst.i.tute for Cancer Research 1997:37173. Obesity, cancer, and estrogen production: See, for instance, Bal ard-Barbash 1999.

Warburg's fermentation work: See Warburg 1956. Tumors starved of fuel: Tannenbaum 1959:530. Footnote. Tannenbaum 1959:524.

Early observations of glucose intolerance in cancer patients: Glicksman et al. 1956. See also Kessler 1971. Unless insulin was added: Temin 1967; Temin 1968. Adrenal and liver-cel cancers: Koontz and Iwahashi 1981. For a review of this research, see Del Giudice et al. 1998. "intensely stimulated...": Heuson et al. 1967:359. "exquisitely sensitive...": Osborne et al. 1976:4539.

Greater number of insulin receptors: Giorgino et al. 1991 ("selective growth...," 452).

The Darwinian model of cancer development: Weinberg 2007: 41324.

Ten thousand tril ion and "enormous opportunity:" Weinberg 1996:252.

Insulin and IGF: For reviews of their roles in cancer development, see Giovannucci 1995; Kaaks 1996; Burroughs et al. 1999; Kaaks and Lukanova 2001; LeRoith and Roberts 2003; Baserga et al. 2003; Pol ak et al. 2004. This section was also informed by interviews with Renato Baserga, Edward Giovannucci, Rudolf Kaaks, Derek LeRoith, Bruce Roberts, and Robert Weinberg.

"stumbled" upon: Interview, Renato Baserga. 216 "strong inhibition...": Baserga 2004.

LeRoith's experiments with IGF-deficient mice: Wu et al. 2002; Wu et al. 2003.

Cheresh has demonstrated: Brooks et al. 1997; interview, David Cheresh.

2003 meeting in London: Interview, Derek LeRoith; Novartis Foundation 2004. Studies linking hyperinsulinemia and IGF to cancer: See Kaaks and Lukanova 2001.

"People were thinking..." and "When applied simultaneously...": Interview, Rudolf Kaaks.

"an environment that favored...": Pol ak et al. 2004.

Live 30 to 50 percent longer: See, for instance, Masoro et al. 1982. For a good review of the history of the calorie-restriction science, see Masoro 2003.

Two possibilities: Masoro 2003.

Harrison's experiments: Harrison et al. 1984 ("Longevities were related"). Whenever these experiments are done: See, for instance, Bertrand et al. 1980.

Oxidative stress, antioxidants, and longevity: Tuma 2001; Weinert and Timiras 2003.

Characteristics of long-lived organisms: Bartke 2002; Davenport 2003.

Genetic studies of yeast: Lin et al. 2000. Worms: Lin et al. 1997. Fruit flies: Clancy et al. 2001. Mice: Holzenberger et al. 2003; Bluher et al. 2003.

"When reduced to essentials...": Bishop 1989.

Longevity mutations regulate dauer state: Kenyon et al. 1993. "The way these worms work...": Interview, Cynthia Kenyon.

Ruvkun reported: Kimura et al. 1997; interview, Gary Ruvkun. Long-lived fruit-fly mutants: Clancy et al. 2001. See also Kenyon 2001.

Gene knockout experiments in mice: Holzenberger et al. 2003. Kahn's research: Bluher et al. 2003; interview, C. Ronald Kahn.

"When food becomes limiting...": Kenyon 2001:168.

Kenyon began a series of experiments: Interview, Cynthia Kenyon.

"Could a low-carb...": Kenyon's slide from her conference presentation. I'm grateful to Professor Kenyon for providing the slides.

Kenyon's restriction of carbohydrate consumption: Interview, Cynthia Kenyon.

"...attendant therapeutic implications...": Farris et al. 2004:1432. "dream of 60 mil ion...": Joslin Diabetes Center 2003. Diabetologists take the same tack: See, for instance, LeRoith 2004 ("normalize" and "intensive...").

NCEP merges both tacks: NCEP 2002 ("atherogenic diet," I -20; "pharmaceutical modification...," I -26).

"Weight sits like a spider...": Wil ett 2001:35. "Excess weight...": Stamler 1962:57.

PART THREE: OBESITY AND THE REGULATION OF WEIGHT.

Epigraphs. "How may the medical...": Stunkard and McClaren-Hume 1959. "To cultivate the faculty...": Tanner 1869a:1.

CHAPTER FOURTEEN:.

THE MYTHOLOGY OF OBESITY.

Epigraph. "A col eague once defined...": Cohen 1989:viii.

"To have our first idea...": Bernard 1957:3233.

"overweight and obesity result...": USDHHS 2001:1.