October 2020 Issue
Cancer Nutrition: Metabolic Syndrome and Cancer — Insights on Their Intersection
By Karen Collins, MS, RDN, CDN, FAND
Vol. 22, No. 8, P. 14
Dietitians know that metabolic syndrome is associated with increased risk of CVD and diabetes. In fact, risk increases more than two-fold and fourfold, respectively.1 What’s less widely known is that metabolic syndrome also increases risk of cancer, cancer recurrence, and cancer mortality.
About 1 in 3 US adults has metabolic syndrome.1,2 It’s defined by the presence of three or more of the following: high blood sugar, high blood pressure, high triglycerides, low HDL cholesterol, and elevated waist circumference. Precise definitions have changed over the years, but most authorities now refer to the “harmonized” criteria developed by a consensus of major international organizations (see table).3,4
In population studies, obesity and overweight are strongly linked to increased risk of at least 12 different cancers.5 Large long-term population studies usually rely on BMI as a practical tool to categorize weight and adiposity.
When working with individuals, how can dietitians identify who’s at increased risk? Researchers say assessments more precise than BMI alone are needed.6 Work is in progress to identify biomarkers of adipose tissue inflammation that could be used in clinical practice to help identify high-risk individuals.
Meanwhile, the link between metabolic syndrome and cancer may provide important clues.
• Metabolic syndrome is associated with a 20% to more than a 60% increase in risk of colorectal, endometrial, liver, pancreatic, and postmenopausal breast cancers.7,8
• Among men with prostate cancer, those with metabolic syndrome are more likely to develop aggressive tumors and experience biochemical recurrence.9
• After a cancer diagnosis, risk of postsurgical complications, recurrence, and mortality is higher among those with metabolic syndrome.1,10
• For survivors of childhood cancers, metabolic syndrome is recognized as a common late effect (depending on the type of cancer and treatment), often with years of latency before it’s seen.11
How Metabolic Syndrome Adds to Risk
Metabolic syndrome often—but not always—occurs in people with overweight or obesity.
• People with overweight or obesity. The use of waist circumference as a criterion for metabolic syndrome identifies people more likely to have excess visceral adiposity and ectopic fat deposition (mainly in the liver, heart, and skeletal muscle). Increased waist circumference in metabolic syndrome also signals likely adipocyte dysfunction, with inflammation, insulin resistance, and dysregulated secretion of hormones and signaling proteins.12 Among National Health and Nutrition Examination Survey (NHANES) participants with overweight or obesity, cancer mortality was significantly higher among those who also met criteria for metabolic syndrome.13
• People with normal BMI. Some people with a BMI categorized as healthy also can have the metabolic issues associated with obesity and thus may face increased cancer risk. Metabolic syndrome despite a normal BMI tends to occur with higher body fat percentage or with greater distribution in visceral (rather than subcutaneous) adipose tissue.13 Visceral adipose tissue plays a large role in hormonal and inflammatory secretions.
Multiple prospective cohort studies have found that among people with normal BMI, those with metabolic syndrome or related metabolic abnormalities, or with elevated waist circumference, had from a 26% increased risk to double the risk of breast or colorectal cancer, and increased cancer mortality compared with individuals who were metabolically healthy.14-16
Mechanisms of Risk
Two key factors in the association of metabolic syndrome with risk and outcomes of cancer are chronic inflammation and insulin resistance.
As adipose tissue outgrows its blood supply, it becomes dysfunctional with immune cell infiltration and chronic low-grade inflammation. Inflammation in this microenvironment—the environment immediately around an adipose tissue cell—triggers signaling pathways and gene expression that promote tumor growth and abnormal physiological changes.6,17 Inflammation enhances production of free radicals that can damage DNA, leading to changes in genes that regulate cell survival and proliferation and cancer progression.10
Inflammation in breast adipose tissue can increase aromatase enzymes, resulting in increased synthesis of estrogen that can promote estrogen-sensitive cancers. In men, cytokines produced by inflamed adipose tissue activate androgen receptors, promoting prostate cancer cell proliferation and survival. And local inflammation can stimulate systemic inflammation throughout the body.6
As adipose tissue capacity to take up and store fatty acids is exceeded, the resulting ectopic fat deposition promotes insulin resistance. Insulin’s ability to inhibit liver glucose production and stimulate glucose uptake by muscle and adipose cells is impaired. Yet normal or near-normal blood sugar levels can be maintained as long as the pancreas can increase insulin secretion.
Insulin resistance doesn’t inhibit insulin’s role in the mitogenic signaling pathway that promotes cell proliferation. Increased insulin production to overcome insulin resistance exaggerates activation of this pathway and increases liver synthesis of insulinlike growth factor-1. The result is enhanced signaling for tumor growth.4,10,17
Fortunately, research shows that adipose inflammation is a reversible process.6 An important question is whether addressing metabolic syndrome can reduce risk and improve outcomes of common cancers.
Implications for Practice
Identifying and supporting diet and lifestyle changes that can improve component risk factors is firstline treatment for metabolic syndrome. Now, studies such as those cited earlier suggest that attention to the pathophysiology signaled by metabolic syndrome means that these steps may play a valuable role in reducing cancer risk. Dietitians can accomplish all of this with the following three strategies.
Advocate Healthful Dietary Patterns
Current debates about the optimal amount of dietary carbohydrate can obscure a clearer conclusion from research about the importance of the quality of carbohydrate-containing food choices. Studies comparing high vs low carbohydrate need to be evaluated carefully: When food selection isn’t controlled, high-carbohydrate diets typically are high in sugars and refined carbohydrates.
Overall dietary patterns, such as a Mediterranean diet or DASH-style pattern, categorized as healthful based on various scoring systems are linked with lower risk of metabolic syndrome and also fit recommendations to reduce cancer risk.18-20 Although these healthful dietary patterns differ, several of their characteristics such as the following are relatively consistent.
• Dietary fiber is associated with lower risk of metabolic syndrome in many, but not all, studies.21 Physiological effects of fibers vary in viscosity, fermentability, and bulking ability, which may explain some variation in these studies (see “Fiber: Increase Amount and Variety” in the July 2018 issue of Today’s Dietitian). For reduction of inflammation and insulin resistance, foods that supply viscous and fermentable fibers are most likely to be beneficial.22,23
• Fruits and vegetables provide more than dietary fiber, as their nutrients and phytocompounds support antioxidant defenses and anti-inflammatory pathways. Greater consumption is linked with lower risk of metabolic syndrome in observational studies.24 Among components of metabolic syndrome, they’re strongly linked with reducing elevated blood pressure. Moreover, fruits and vegetables are low in calorie density and therefore may help avoid weight gain that can trigger metabolic syndrome and promote obesity-related cancers.25
• Pulses, whole grains, and nuts also contribute unique nutrients, phytocompounds, and gut microbiota support that add to the protection against metabolic syndrome seen in Mediterranean and other plant-forward eating patterns.
• Fish consumption is associated with lower risk of metabolic syndrome in prospective cohort studies.26 This may reflect influence of increased omega-3 fatty acid consumption, and also may be a marker of an overall healthful dietary pattern.
There are many different ways to create this kind of eating pattern and show potential to promote overall metabolic health. When linking metabolic health with lower cancer risk, the New American Plate approach, developed by the American Institute for Cancer Research, can be helpful to connect the dots.
Troubleshoot Western Dietary Patterns
Diets high in sweets, refined grains, sugar-sweetened beverages, and red and processed meats are associated with greater risk of metabolic syndrome.18
• Sugar-sweetened beverages are linked with greater incidence of metabolic syndrome, in some cases even independent of total daily calorie intake.27
• Ultraprocessed foods may contribute to metabolic syndrome through effects on
hypertension and weight gain and waist circumference. In a cross-sectional analysis of NHANES participants, after adjusting for confounding variables, people with highest consumption of ultraprocessed foods (>71% of calories) had 28% higher prevalence of metabolic syndrome than people who consumed <40% of calories from ultraprocessed foods.28
Encourage Lifestyle Changes
• Seek small wins to avoid weight gain. As noted, metabolic syndrome is strongly linked to adiposity, especially excess visceral fat. A large prospective cohort study found that weight gain of 5% or more over nine years of follow-up was associated with increased development of metabolic syndrome among normal-weight adults.29
• Promote daily physical activity and separate it from weight. Even with no change in weight, regular physical activity can help avoid unhealthful elevations of insulin and reduce inflammation. People who get regular physical activity are less likely to develop metabolic syndrome. And getting more than the general recommendation of 150 minutes of moderate activity per week reduces risk even further.30
In a clinical trial involving breast cancer survivors who were sedentary or had overweight or obesity, a program that combined moderate to vigorous aerobic activity and resistance exercise successfully reduced metabolic syndrome and improved biomarkers related to metabolic syndrome and cancer.31
• Support sleep habits. Emerging evidence associates lack of adequate sleep (generally less than seven hours per night on a regular basis) with increased markers of inflammation and insulin resistance. Sleep deprivation and late waking hours may contribute to metabolic syndrome through effects on eating habits and circadian rhythm disruption.32
Communicating Essential Messages
Many members of the public are unfamiliar with the concept of metabolic syndrome,1 and many misunderstandings remain about diet and other lifestyle choices that can reduce cancer risk and improve outcomes for cancer survivors. This provides a valuable opportunity for dietitians to discuss unifying concepts about eating patterns that promote good health.
With regard to metabolic health, discussing insulin resistance provides a chance to clarify that normal blood sugar doesn’t guarantee absence of underlying harm. Individual factors such as blood sugar numbers and blood pressure readings are more than “just a number.” Especially when considered together, they provide a big picture view of health.
Overweight and obesity, assessed by weight and BMI, identify people at greater risk of cancer (and other chronic diseases), but these are imperfect tools. Maintaining an individually healthy weight can reduce the metabolic effects that unhealthful amounts and types of body fat produce. And aiming for eating patterns, physical activity, and lifestyle habits that support metabolic health provides a path likely to reduce cancer risk while promoting overall health.
— Karen Collins, MS, RDN, CDN, FAND, is a nutrition consultant specializing in cancer prevention and cardiometabolic health, and nutrition advisor to the American Institute for Cancer Research.
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