Metabolic syndrome—a cluster of risk factors that accelerates the onset of cardiovascular disease and certain cancers—is a high priority for nutritional intervention and prevention of chronic disease. Diagnostic criteria include hypertension, dyslipidemia, and excess visceral or intra-abdominal fat. Insulin resistance, a pre-diabetic state that underlies metabolic syndrome, is closely linked with obesity. In 1988, Gerald Reaven, M.D., Professor Emeritus of Medicine at Stanford University, first described the syndrome. Today the condition affects 23.7% of U.S. adults, or approximately 50 million people.

Obesity in and of itself is a major risk factor for cancer. Outcomes from a prospective cancer prevention study indicate that overweight and obesity account for 14% of all cancer deaths in men and 20% of those in women. Data show significant positive associations between obesity and higher death rates from the following cancers: esophageal; colon and rectum; liver; gallbladder; pancreas; kidney; stomach (in men); prostate; breast; uterus; cervix; and ovary. Calle et al., the authors of the study, estimate that over 90,000 cancer deaths per year could be avoided if adults maintained a normal body weight (BMI < 25).

Obesity is implicated in the etiology and progression of cancer at multiple cancer sites via signaling pathways that regulate key functions, including cancer cell proliferation, apoptosis, metastasis, and angiogenesis. Most obese individuals are insulin-resistant, a condition that may result from a defect in the oxidation and storage of fatty acids in the liver and skeletal muscle. Impaired fatty acid oxidation, mitochondrial dysfunction, and altered serum concentrations of adipocytokines such as adiponectin and TNF-alpha contribute to the development of insulin resistance. Because insulin resistance decreases sensitivity to insulin, the body compensates by secreting more insulin to maintain glucose homeostasis. The result is compensatory hyperinsulinemia. Evidence links chronic hyperinsulinemia to greater risk of cancers of the colon, endometrium, and other sites. Elevated serum insulin concentrations increase the bioavailability of insulin-like growth factor-I (IGF-I), which also plays a critical role in carcinogenesis and tumorigenesis.

Successful interventions for weight loss and maintenance at the individual and community levels are needed to reduce cancer risk. Substantive experimental and epidemiologic evidence provide strong support for the association between dietary choices, weight control, and cancer. A number of studies show onset of cancer in the colon, mammary glands, and prostate of mice fed a Western-style diet. Experimental animal studies have also directly associated dietary intake of saturated and trans fat with the elevation of circulating triglycerides and cholesterol. According to findings from the Women’s Intervention Study (WINS), a low-fat dietary intervention cut risk of breast cancer recurrence in post-menopausal women by 24%. Such research, coupled with the emerging field of genetics and metabolomics, will enable identification of nutritional phenotypes and development of individualized dietary recommendations for the prevention and treatment of chronic disease.