Consequences of Obesity
Obese individuals have higher levels of inflammatory markers. Sustained, low-level inflammation has been implicated in the pathogenesis of several significant diseases, including heart disease, cancer, diabetes, and Alzheimer’s disease (Hartaigh 2012; Touvier 2013; Cruz 2012; Holmes 2012). Fat tissue can act much like an endocrine (hormonal) gland, storing and secreting hormones and cytokines (signaling proteins involved in triggering the inflammatory response) into circulation and affecting metabolism throughout the body. Abdominal visceral fat cells may produce inflammatory molecules such as tumor necrosis factor alpha (TNF-α) and interleukin-6 at levels sufficient to induce an inflammatory response (Trayhurn 2005; Schrager 2007). In overweight individuals, abdominal fat cells may be producing up to 35% of the total interleukin-6 in the body (Mohamed-Ali 1997). Fat tissue can also be infiltrated by macrophages (cells of the immune system that mediate inflammation), which secrete pro-inflammatory cytokines. This accumulation of macrophages appears to be proportional to BMI, and may be a major cause of low-grade, systemic inflammation and insulin resistance in obese individuals (Ortega Martinez de Victoria 2009; Weisberg 2003).
Obesity is a risk factor for several types of cancer. White adipose tissue (ie, “bad fat”) can secrete a variety of hormones and growth factors that may stimulate cancer cell growth. Experimental cancer models in animals suggest that tumors may recruit healthy cells from elsewhere in the body (including white fat) to build the blood vessels critical for the progression of tumor growth (Zhang 2009).
Postmenopausal breast cancer risk increases with obesity, possibly through effects on systemic inflammation, or increases in circulating insulin and insulin-like growth factor 1 (IGF-1), both of which can promote tumor growth (Brown 2012). Obesity increases gastric and esophageal cancer risk; mechanisms for this also include increased insulin and IGF-1 signaling, as well as increased incidence of gastroesophageal reflux disease (GERD) (Li 2012). Population studies have implicated obesity as a risk factor for liver cancer (hepatocellular carcinoma). Along with obesity, nonalcoholic fatty liver disease (NAFLD), an increase in fat stores in the liver, is a hallmark of metabolic syndrome; the inflammation and liver fibrosis associated with fatty liver can progress into hepatocellular carcinoma (Shen 2012). Central obesity has been reported as a risk factor for colorectal cancer. Comprehensive reviews have estimated that colorectal cancer risk increases by 7% as BMI increases by 2 points, or 5% for each inch of waist circumference above normal (Sung 2011). Again, circulating growth factors and inflammatory cytokines are thought to contribute to the increase in abnormal cell proliferation. Some evidence suggests that the satiety hormone leptin may also play a role in colorectal cancer progression; cell culture studies have shown that leptin can increase the growth and proliferation of colon adenocarcinoma cells (Jaffe 2008).
Obesity may increase thyroid cancer risk; the rise in thyroid cancer incidence parallels that of obesity, although studies that explore the relationship between these two diseases have conflicting results (Fröhlich 2012). The effect of obesity on thyroid cancer may be due to increased insulin/IGF-1 expression; thyroid stimulating hormone levels are sensitive to insulin and IGF-1 levels, and all three hormones work together to stimulate thyroid activity. Increases in IGF-1 have been correlated with increased thyroid tumor diameter, and insulin resistance has been shown to be more frequent in thyroid cancer patients than in cancer-free controls (Mijovic 2011).
Insensitivity of tissues to circulating insulin (ie, insulin resistance) is a hallmark of type 2 diabetes and metabolic syndrome and has obesity as a major risk factor. While moderate post-meal increases in insulin are normal and signal tissues to take up glucose and store it as glycogen and fat, overconsumption can lead to accelerated increases in fat mass and excessive insulin production (ie, hyperinsulinemia). Sustained hyperinsulinemia activates inflammatory pathways, which can lead to insulin resistance; although the mechanisms of this phenomenon are not clearly understood (Sung 2011; Bastard 2006). The appetite suppressing activity of insulin may be abolished in insulin-resistant obese individuals (Hagobian 2010), which may promote further weight gain by removing this important appetite control mechanism.
High Blood Pressure
Increased blood pressure elevates the risk of several other diseases, including artherosclerosis, heart attack, heart failure, stroke, chronic kidney disease, and vision loss (Kones 2010; Emerging Risk Factors Collaboration 2010; Schnohr 2002). Excessive adipose tissue can increase blood pressure by several possible mechanisms: aside from its effect on inflammation, fat cells can be a source of the hypertensive proteins renin and angiotensinogen, and angiotensin converting enzyme, all of which work together to increase blood pressure by promoting water retention and causing constriction of blood vessels (Nguyen 2012b). Fat tissue also produces the satiety hormone leptin, which, in combination with the renin-angiotensin and sympathetic nervous systems, may influence blood pressure by causing the kidneys to retain sodium and water; high leptin levels are also related to insulin resistance, itself a risk factor for hypertension (Nguyen 2012b; Naumnik 2010). Compared to normal weight individuals, overweight individuals are 1.7 times as likely to have hypertension, while for obese individuals, the risk is 2.6-fold (Nguyen 2008). A BMI between 18.5 and 24.9 carries the lowest risk of hypertension. Reductions of systolic blood pressure by 5-20 mmHg per 22 pounds of weight loss have been observed in several studies (The Trials of Hypertension Prevention Collaborative Research Group 1997; He 2000).
Excess weight puts additional mechanical stress on the joints. Obesity has been unequivocally associated with osteoarthritis risk, particularly in weight-bearing joints such as the knee and hip. In an analysis of 21 studies on obesity and knee osteoarthritis incidence, a 5 point increase in BMI was associated with a 35% increase in osteoarthritis risk; this effect was more significant in women than men (38% versus 22%, respectively) (Jiang 2012).
Gastroesophageal Reflux Disease
Gastroesophageal reflux disease (GERD) is a condition that develops when the reflux of stomach contents into the esophagus causes troublesome symptoms (heartburn) and/or complications (esophageal cancer) (Vakil 2006). Increased body mass and abdominal adiposity increases pressure on the stomach and lower esophagus. This can stress the lower esophageal valve, which is responsible for retaining acid in the stomach. When this valve is compromised, it loses its ability to maintain a seal against gastric reflux. Sustained abdominal pressure due to central obesity can also increase risk of hiatal hernia (the forcing of part of the stomach above the diaphragm into the chest cavity), another risk factor for gastric reflux (Festi 2009). Among 7 studies that examined the relationship between body mass and GERD complications, overweight individuals averaged a 43% increase, and obese individuals a 94% increase, in GERD symptoms over individuals with a normal body mass (Hampel 2005). Exposure to stomach acid also increases the rate of neoplastic alterations (abnormal cellular proliferation) within the esophagus, leading to the higher incidence of esophageal adenocarcinoma observed in overweight individuals in most of these studies.
Obesity is the strongest contributor to obstructive sleep apnea, a breathing disorder that occurs during sleep and causes symptoms ranging from restless sleep to low blood oxygen (hypoxemia). About 70% of people with obstructive sleep apnea are obese, and about 40% of obese individuals have sleep apnea. Among individuals with BMIs over 60, the prevalence of sleep apnea is 90%. Obese individuals are more likely to suffer from night eating syndrome or sleep-related eating disorder, disorders characterized by symptoms ranging from excessive nighttime hunger to unconscious nocturnal eating. The prevalence of these eating disorders among obese persons is 6–16%, as compared to 1.5% in the general population. Narcolepsy (excessive daytime sleepiness) is also more common in obese individuals (Akinnusi 2012).
Poor sleep quality is more than just a consequence of obesity. Rather, a vicious cycle in which obesity leads to impaired sleep leads to increased appetite leads to obesity may complicate weight loss efforts for many individuals. Studies show that sleep deprivation, as can occur when one’s sleep is suboptimal due to obesity-related phenomena such as sleep apnea, is associated with increased appetite (Knutson 2007). In an insightful magnetic resonance imaging experiment, researchers showed that a brain region called the anterior cingulate cortex appears to be more responsive to anticipation of food following sleep deprivation as compared to a full-night of sleep. Increased neural activity in this brain region is associated with obesity, and its level of activation correlated with appetite in this study (Benedict 2012). Thus, improving sleep hygiene and ensuring that restful, restorative sleep is attained is an integral aspect of successful weight loss. A number of strategies for improving sleep quality are discussed in the Insomnia protocol.