c. Cancer
Approximately 1.2 million new cases of cancer are diagnosed each year. 28 During the
past decade, several case-control and prospective cohort studies have been published which
document the risk that overweight individuals have of developing certain types of cancers. One
report, which was published in Lancet Oncology in 2002, shows that the risk of cancer increases
with increasing BMI.29 Another review undertaken by the International Agency for Research on
Cancer summarized the links between overweight, obesity, and cancer risk based on a
comprehensive evaluation of epidemiological studies published in the scientific literature. That
report, which appeared in Nature in 2004, concluded that those who are overweight are at
increased risk of developing several types of cancer, including colon cancer (RR, 1.5 for men,
1.2 for women), postmenopausal breast cancer in women (RR, 1.3), endometrial cancer (RR, 2.0),
kidney cancer (RR, 1 .5), esophageal adenocarcinoma (RR, 2.0), pancreatic cancer (RR, 1.3),
gallbladder cancer (RR, 1.5), and gastric cardiac adenocarcinoma (RR, 1.5).3° These results
were, just recently, corroborated by the American Institute for Cancer Research.31
The association between overweight and an increased risk of mortality from cancer was
further established based on data from a prospective study of a large cohort of U.S. adults
(“Cancer Prevention Study II”).3z In that study, which was published in the New England
Journal of Medicine in 2003, the authors reported that overweight women had a significantly
elevated risk of death from all types of cancers (RR, 1.08). They also documented an increased
risk for certain types of cancer, including colorectal cancer (RR, 1.10), breast cancer (RR, 1.34),
uterine cancer (RR, 1.50), ovarian cancer (RR, 1.15), kidney cancer (RR, 1.33), and non-
Hodgkin’s lymphoma (RR, 1.22). Overweight men were also found to have significantly
elevated risks of colorectal cancer (RR, 1.20), pancreatic cancer (RR, 1.13), prostate cancer (RR,
1.08), kidney cancer (RR, 1.18), multiple myeloma (RR, 1.18), and leukemia (RR, 1.14). On the
basis of these findings, the authors of this study estimated that more than 90,000 cancer-related
deaths could be prevented each year if all adults had a BMI of less than 25 throughout their lives.
Mookadam F, Lopez-Jiminez F. Association of bodyweight with total mortality and with cardiovascular events in
coronary artery disease: a systematic review of cohort studies. Lancet 2006;368:666-78. (Exh. 18).
27 Baker JL, Olsen LW, Sorensen, TI. Childhood body-mass index and the risk of coronary heart disease in
adulthood. N Engl J Med 2007;357:2329-37. (Exh. 19).
28
Centers for Disease Control and Prevention. NCHS Data on Cancer. (Accessed January 3, 2008, at
http://www.cdc.gov/nchs/data/factsheets/cancer.pdf).
29
Bianchini F, Kaaks R, Vainio H. Overweight, obesity, and cancer risk. Lancet Oncol 2002;3:565-74. (Exh. 20).
30
Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nature
2004;4:579-91. (Exh. 21).
31
World Cancer Research Fund; American Institute for Cancer Research. Food, nutrition, physical activity, and the
prevention of cancer: a global perspective. Washington, DC: American Institute for Cancer Research, 2007. Chapter
6.1, Body composition, growth, and development: body fatness; p. 210-28. (Exh. 22). This report concluded that
being overweight increases the risk of esophageal adenocarcinoma, pancreatic cancer, colorectal cancer,
postmenopausal breast cancer, endometrial cancer, and kidney cancer. In addition, the evidence indicated a very
probable association between being overweight and gallbladder cancer.
32
Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a
prospectively studied cohort of U.S. adults. N Engl J Med 2003;348:1625-38. (Exh. 23).
d. Obesity
As mentioned at the outset, the proportion of Americans who are obese has increased at
an alarming rate in recent years. Between 1980 and 2002, the prevalence of obesity among
adults doubled in the United States and it is currently estimated at 32% of the population. 3
Individuals who are obese were at one time overweight, and research confirms that the
progression from overweight to obesity is quite common. Thus, overweight is an independent
risk factor for obesity. In a prospective, cohort study examining weight trends in over 9,000
young adults followed for 20 years, being mildly or moderately overweight at ages 20-22 was
linked with a substantial incidence of obesity by ages 35-37.34 For example, 41% of white, 47%
of Hispanic, and 66% of black women who had a BMI of 24-25 at ages 20-22 became obese by
ages 35-37. Among women who had a BMI of 26-27.9 at 20-22 years of age, approximately
80% became obese by ages 35-37, regardless of racial or ethnic group. Therefore, overweight
individuals are also at increased risk of obesity as they age.
2. Recent Studies of Pathophysiological Mechanisms Also Confirm
That Being Overweight Is a Significant Risk Factor for Disease
In addition to the epidemiological studies cited above, there have also been numerous
investigations during the past decade of the cellular and molecular mechanisms associated with
adipose tissue. These studies further confirm, and provide an underlying physiological basis for,
the finding that overweight is a significant risk factor for various diseases. Until recently, fat
tissue was thought of mainly as a passive storehouse of energy. During the recent past, however,
major scientific strides have clarified the dynamic role that adipose tissue plays in the etiology
and maintenance of chronic inflammation associated with type 2 diabetes, cardiovascular disease,
and cancer. 35 Indeed, chronic low-grade inflammation has been directly implicated in the
pathogenesis of both cancer and cardiovascular disease. As described briefly below, researchers
believe that chronic inflammation associated with weight gain helps explain the link between
overweight and an increased risk of disease. 36
33
Flegal KM, Carroll MD, Ogden CL, Johnson CL. Prevalence and trends in obesity among US adults, 1999-2000.
JAMA 2002;288:1723-7. (Exh. 24); Hedley AA, Ogden CL, Johnson CL, Carroll MD, Curtin LR, Flegal KM.
Prevalence of overweight and obesity among US children, adolescents, and adults, 1999-2002. JAMA
2004;291:2847-50. (Exh. 25); Ogden CL, et al. Prevalence of overweight and obesity in the United States, 1999-
2004. JAMA 2006;295:1549-55. (Exh. 1).
34 McTigue KM, Garrett JM, Popkin BM. The natural history of the development of obesity in a cohort of young
U.S. adults between 1981 and 1998. Ann Intern Med 2002;136:857-64. (Exh. 26).
35
For example, investigators have found that adipose tissue secretes a large number of proteins – adipokines – that
act in an autocrine, paracrine, or endocrine fashion to control various metabolic functions. See Greenberg A, Obin
M. Obesity and the role of adipose tissue in inflammation and metabolism. Am J Clin Nutr 2006;83(Suppl):461 S-
5S. Fat cell production of pro-inflammatory cytokines, such as interleukin-6 and tumor necrosis factor-or (TNF), and
adipocytokines, such as adiponectin and leptin, are also important for many aspects of inflammation and immunity.
See Tolg H, Moschen A. Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nature
2006;6:772-83; Van Gaal L, Mertens I. Mechanisms linking obesity with cardiovascular disease. Nature
2006;444:875-80.
36
Fogarty AW, Glancy C, Jones S, et al. A prospective study of weight change and systemic inflammation over 9
years. Am J Clin Nutr 2008;87:30-5.
Several studies over the past ten years of overweight individuals have shown a significant
increase in systemic inflammation as indicated by increases in acute-phase-C-reactive protein
(“CRP”), a marker for chronic inflammation. 37 For example, during a nine year period, a linear
association was observed between an increase in weight and serum CRP, with a one kg
increment in weight gain resulting in an additional increase in CRP of 0.09 mg/L.38 In addition,
a recent study of middle-aged men found that those who reported a weight increase averaging
approximately 15 pounds over a 10 yr period expressed more oxidative injury and inflammation
in skeletal muscle compared with subjects that maintained a stable body weight over the same
time period.39 Thus, even mild accretion of adipose tissue is associated with oxidative stress and
inflammation in human muscle. On the other hand, recent studies suggest that the benefits of
calorie-restriction can likely be attributed to reduced fat stores and an accompanying decrease in
the concentration of fat-derived peptides, such as cytokines, complement factors and substrates. 40
The foregoing studies of the biochemistry involving inflammation and adipose issue have
been further supplemented by imaging studies during the past decade. Computer tomography
scans and magnetic resonance imaging now allow investigators to measure specific adipose
tissue deposits in the human body. Utilizing these techniques, scientists have examined the
relationship of these different types of adipose tissue, including abdominal subcutaneous adipose
tissue and visceral adipose tissue, to insulin resistance, metabolic syndrome, and the development
of type 2 diabetes and clinical cardiovascular events. These studies have found that changes in
body composition – that is, the distribution of different types of adipose tissue and the ratio of fat
free mass to fat mass – may significantly impact the risk of cardiovascular disease, type 2
diabetes and cancer in overweight individuals. 41
Specifically, work in this area has focused primarily on central fat distribution and, in
particular, visceral adiposity. Despite the smaller size of the visceral adipose tissue depot, which
is found in the deeper tissues and around the organs, many investigations have demonstrated that
visceral adipose tissue mass is significantly correlated with insulin resistance, type 2 diabetes,
and cardiovascular events.
42
Although there is some disagreement among investigators as to
whether visceral adiposity or abdominal subcutaneous adiposity is the primary cause of the
increased risk, there is no question that there is increasingly strong evidence that fat accumulated
37 See, e.g., Visser M, Bouter L, McQuillan GM, Wener MH, Harris TB. Elevated C-reactive protein levels in
overweight and obese adults. JAMA 1999;282:2131-5; Koenig W, Sund M, Frohlich M, et al. C-reactive protein, a
sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy
middle-aged men. Circulation 1999;99:237-42.
38 Fogarty AW, Glancy C, Jones S, et al. A prospective study of weight change and systemic inflammation over 9
years. Am J Clin Nutr 2008;87:30-5; see also Bogers RP, Bemelmans WJ, Hoogenveen RT. Association of
overweight with increased risk of coronary heart disease partly independent of blood pressure and cholesterol levels:
a meta-analysis of 21 cohort studies including more than 300,000 persons. Arch Intern Med 2007;167:1720-8.
39
de la Maza M, Olivares D, Hirsch S, et al. Weight increase and overweight are associated with DNA oxidative
damage in skeletal muscle. Clin Nutr 2006;25:968-76.
40
Barzilai N, Gupta G. Revisiting the role of fat mass in the life extension induced by caloric restriction. J Gerontol
A Biol Sci Med Sci 1999;54:890-96.
41 Lebovitz H, Banerji M. Point: visceral adiposity is causally related to insulin resistance diabetes care.
2005;28:2321-5.
42
Id.; see also references 9-11, 13, 14, 16, 19, and 20.
in the trunk should be considered harmful .43 Even in non-obese subjects, abdominal fat
accumulation is correlated with glucose intolerance, hyperlipemia, and hypertension. 4′ Thus, in
addition to the epidemiological studies summarized above, biochemical and imaging studies
from the past decade further confirm the increased risk that results from being overweight.
B. OVERWEIGHT AMERICANS WHO SEEK TO REDUCE THEIR RISK OF DISEASE ARE
BEING DIVERTED FROM EFFECTIVE WAYS TO LOSE WEIGHT BY EXAGGERATED AND
UNSUBSTANTIATED CLAIMS ACCOMPANYING WEIGHT LOSS SUPPLEMENTS
1. Consumer Survey Data Confirm That Individuals Understand the Health
Risks of Being Overweight and Many Use Dietary Supplements to Lose
Weight
As the above-referenced scientific reports and studies have appeared over the past decade,
the link between being overweight and an increased risk of developing a serious disease has
become much more firmly planted in the public’s mind. As the results from these studies have
been published, there have been concomitant publications in the media, including the popular
press, that have described the increased risks of being overweight, including diabetes, 5
cardiovascular disease, 46 cancer,
47
and other maladies. 48 At the same time, this information has
likely been conveyed directly to overweight individuals during visits with their physicians. As a
result, many Americans now understand the adverse health consequences and risks of disease
that may result from being overweight.
” See de Simon G, Devereux R, Kizer J, et al. Body composition and fat distribution influence systemic
hemodynamics in the absence of obesity: the HyperGEN Study. Am J Clin Nutr 2005;81:757-61; Freedland E. Role
of a critical visceral adipose tissue threshold (CVATT) in metabolic syndrome: implications for controlling dietary
carbohydrates: a review. Nutr & Metab 2004;1:1-12; Miles JM, Jensen MD. Counterpoint: visceral adiposity is not
causally related to insulin resistance. Diabetes Care 2005;28:2326.
44
Singh RB, Rastogi SS, Niaz MA, Postiglione A. Association of central obesity and insulin resistance with high
prevalence of diabetes and cardiovascular disease in an elderly population with low fat intake and lower than normal
prevalence of obesity: the Indian paradox. Coron Artery Dis 1998;9:559-65.
45
See, e.g., Stein R. Fitness over thinness for hearts: but another study cites diabetes risk for overweight women.
Washington Post. September 8, 2004:A03; Parker-Pope T. Another reason to lose weight: doctors struggle to convey
risks of diabetes. Wall Street Journal. September 23, 2003:D1; Manning A. Overweight kids may be at risk for
diabetes. USA Today. March 14, 2002:8D.
46
See e.g., Nagourney E. Vital signs: at risk; weight as a formula for a stroke. New York Times. December 17,
2002:F8; Maugh TH II. The nation; slight weight gain found to increase heart failure risk; science: a study says that
putting on as little as four pounds can be dangerous to health. Los Angeles Times. August 1, 2002:16; Okie S. Study
links excess weight to risk of heart failure. Washington Post. August I, 2002:A02.
47 See e.g., Brody J. Personal health: another study finds a link between excess weight and cancer. New York Times.
May 6, 2003:F7; Armstrong D. Obesity is linked to cancer deaths: study finds Americans raise their risk of dying by
being too overweight. Wall Street Journal. April 24, 2003:D3; Hellmich N. Being overweight linked to dying of
cancer. USA Today. April 24, 2003:1A; Fackelmann K. Breast cancer risk rises with weight gain. USA Today. April
9, 2002:8D.
48 See e.g., Marchione M. Overweight kids at risk of fractures, study shows. Washington Post. November 22,
2005:A11; Extra body weight can be hard on the knees: overweight people are at a greater risk for cartilage damage,
which may require surgery. Los Angeles Times. June 6, 2005:F8; Stein R Study links excess weight to likelihood of
Alzheimer’s: risk increases in women overweight at 70. Washington Post. July 15, 2003:A01; Hellmich N. Extra
weight shaves years off lives. USA Today. January 7, 2003: IA.
That was precisely the finding of an extensive consumer survey – “The Landmark
Survey” – conducted by the Center for Survey and Research Analysis at the University of
Connecticut in collaboration with the Center for Weight Loss at the University of
Pennsylvania.49 The results of that study were presented a the 2006 Annual Scientific Meeting
of the North American Association for the Study of Obesity
50

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